TY  - JOUR
AU  - Tomić Vujović, Kristina
AU  - Ugrin, Milena
AU  - Tošić, Nataša
AU  - Vuković, Vojin
AU  - Marjanović, Irena
AU  - Kostić, Tatjana
AU  - Stanković, Sanja
AU  - Otasević, Vladimir
AU  - Sarać, Sofija
AU  - Antić, Darko
AU  - Pavlović, Sonja
AU  - Karan-Đurasević, Teodora
PY  - 2024
UR  - https://www.mdpi.com/1422-0067/25/2/922
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/2318
AB  - Dysregulated expression of the long non-coding RNA MALAT1 has been implicated in the pathogenesis and progression of a variety of cancers, including hematological malignancies, but it has been poorly investigated in chronic lymphocytic leukemia (CLL). In this study, the expression of MALAT1 was measured using a quantitative reverse-transcriptase polymerase chain reaction in the peripheral blood mononuclear cells of 114 unselected, newly diagnosed CLL patients in order to analyze its association with clinical, laboratory, and molecular patients’ characteristics at diagnosis, as well as its prognostic relevance. MALAT1 was found to be upregulated in CLL patients in comparison to healthy controls, and expression levels were not related to age, leukocyte, lymphocyte and platelet count, serum β2-microglobulin, and IGHV somatic hypermutational status. On the other hand, high MALAT1 expression was associated with several favorable prognostic markers (high hemoglobin, low serum lactate dehydrogenase, earlier clinical stages, CD38-negative status), but also with unfavorable cytogenetics. Furthermore, an association between high MALAT1 levels and longer time to first treatment and overall survival in IGHV-unmutated CLL subtype was observed. In summary, our results imply that high MALAT1 expression at diagnosis may be a predictor of better prognosis and point to MALAT1 expression profiling as a candidate biomarker potentially useful in clinical practice.
PB  - MDPI
T2  - International Journal of Molecular Sciences
T1  - Expression Pattern and Prognostic Significance of the Long Non-Coding RNA Metastasis-Associated Lung Adenocarcinoma Transcript 1 in Chronic Lymphocytic Leukemia
IS  - 2
SP  - 922
VL  - 25
DO  - 10.3390/ijms25020922
ER  - 

@article{
author = "Tomić Vujović, Kristina and Ugrin, Milena and Tošić, Nataša and Vuković, Vojin and Marjanović, Irena and Kostić, Tatjana and Stanković, Sanja and Otasević, Vladimir and Sarać, Sofija and Antić, Darko and Pavlović, Sonja and Karan-Đurasević, Teodora",
year = "2024",
abstract = "Dysregulated expression of the long non-coding RNA MALAT1 has been implicated in the pathogenesis and progression of a variety of cancers, including hematological malignancies, but it has been poorly investigated in chronic lymphocytic leukemia (CLL). In this study, the expression of MALAT1 was measured using a quantitative reverse-transcriptase polymerase chain reaction in the peripheral blood mononuclear cells of 114 unselected, newly diagnosed CLL patients in order to analyze its association with clinical, laboratory, and molecular patients’ characteristics at diagnosis, as well as its prognostic relevance. MALAT1 was found to be upregulated in CLL patients in comparison to healthy controls, and expression levels were not related to age, leukocyte, lymphocyte and platelet count, serum β2-microglobulin, and IGHV somatic hypermutational status. On the other hand, high MALAT1 expression was associated with several favorable prognostic markers (high hemoglobin, low serum lactate dehydrogenase, earlier clinical stages, CD38-negative status), but also with unfavorable cytogenetics. Furthermore, an association between high MALAT1 levels and longer time to first treatment and overall survival in IGHV-unmutated CLL subtype was observed. In summary, our results imply that high MALAT1 expression at diagnosis may be a predictor of better prognosis and point to MALAT1 expression profiling as a candidate biomarker potentially useful in clinical practice.",
publisher = "MDPI",
journal = "International Journal of Molecular Sciences",
title = "Expression Pattern and Prognostic Significance of the Long Non-Coding RNA Metastasis-Associated Lung Adenocarcinoma Transcript 1 in Chronic Lymphocytic Leukemia",
number = "2",
pages = "922",
volume = "25",
doi = "10.3390/ijms25020922"
}

Tomić Vujović, K., Ugrin, M., Tošić, N., Vuković, V., Marjanović, I., Kostić, T., Stanković, S., Otasević, V., Sarać, S., Antić, D., Pavlović, S.,& Karan-Đurasević, T.. (2024). Expression Pattern and Prognostic Significance of the Long Non-Coding RNA Metastasis-Associated Lung Adenocarcinoma Transcript 1 in Chronic Lymphocytic Leukemia. in International Journal of Molecular Sciences
MDPI., 25(2), 922.
https://doi.org/10.3390/ijms25020922

Tomić Vujović K, Ugrin M, Tošić N, Vuković V, Marjanović I, Kostić T, Stanković S, Otasević V, Sarać S, Antić D, Pavlović S, Karan-Đurasević T. Expression Pattern and Prognostic Significance of the Long Non-Coding RNA Metastasis-Associated Lung Adenocarcinoma Transcript 1 in Chronic Lymphocytic Leukemia. in International Journal of Molecular Sciences. 2024;25(2):922.
doi:10.3390/ijms25020922 .

Tomić Vujović, Kristina, Ugrin, Milena, Tošić, Nataša, Vuković, Vojin, Marjanović, Irena, Kostić, Tatjana, Stanković, Sanja, Otasević, Vladimir, Sarać, Sofija, Antić, Darko, Pavlović, Sonja, Karan-Đurasević, Teodora, "Expression Pattern and Prognostic Significance of the Long Non-Coding RNA Metastasis-Associated Lung Adenocarcinoma Transcript 1 in Chronic Lymphocytic Leukemia" in International Journal of Molecular Sciences, 25, no. 2 (2024):922,
https://doi.org/10.3390/ijms25020922 . .

TY  - JOUR
AU  - Tomić Vujović, Kristina
AU  - Ugrin, Milena
AU  - Tošić, Nataša
AU  - Vuković, Vojin
AU  - Marjanović, Irena
AU  - Kostić, Tatjana
AU  - Stanković, Sanja
AU  - Otašević, Vladimir
AU  - Šarac, Sofija
AU  - Antić, Darko
AU  - Pavlović, Sonja
AU  - Karan-Đurašević, Teodora
PY  - 2024
UR  - https://www.mdpi.com/1422-0067/25/2/922
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/2310
AB  - Dysregulated expression of the long non-coding RNA MALAT1 has been implicated in the pathogenesis and progression of a variety of cancers, including hematological malignancies, but it has been poorly investigated in chronic lymphocytic leukemia (CLL). In this study, the expression of MALAT1 was measured using a quantitative reverse-transcriptase polymerase chain reaction in the peripheral blood mononuclear cells of 114 unselected, newly diagnosed CLL patients in order to analyze its association with clinical, laboratory, and molecular patients’ characteristics at diagnosis, as well as its prognostic relevance. MALAT1 was found to be upregulated in CLL patients in comparison to healthy controls, and expression levels were not related to age, leukocyte, lymphocyte and platelet count, serum β2-microglobulin, and IGHV somatic hypermutational status. On the other hand, high MALAT1 expression was associated with several favorable prognostic markers (high hemoglobin, low serum lactate dehydrogenase, earlier clinical stages, CD38-negative status), but also with unfavorable cytogenetics. Furthermore, an association between high MALAT1 levels and longer time to first treatment and overall survival in IGHV-unmutated CLL subtype was observed. In summary, our results imply that high MALAT1 expression at diagnosis may be a predictor of better prognosis and point to MALAT1 expression profiling as a candidate biomarker potentially useful in clinical practice.
PB  - MDPI
T2  - International Journal of Molecular Sciences
T2  - International Journal of Molecular Sciences
T1  - Expression Pattern and Prognostic Significance of the Long Non-Coding RNA Metastasis-Associated Lung Adenocarcinoma Transcript 1 in Chronic Lymphocytic Leukemia
IS  - 2
SP  - 922
VL  - 25
DO  - 10.3390/ijms25020922
ER  - 

@article{
author = "Tomić Vujović, Kristina and Ugrin, Milena and Tošić, Nataša and Vuković, Vojin and Marjanović, Irena and Kostić, Tatjana and Stanković, Sanja and Otašević, Vladimir and Šarac, Sofija and Antić, Darko and Pavlović, Sonja and Karan-Đurašević, Teodora",
year = "2024",
abstract = "Dysregulated expression of the long non-coding RNA MALAT1 has been implicated in the pathogenesis and progression of a variety of cancers, including hematological malignancies, but it has been poorly investigated in chronic lymphocytic leukemia (CLL). In this study, the expression of MALAT1 was measured using a quantitative reverse-transcriptase polymerase chain reaction in the peripheral blood mononuclear cells of 114 unselected, newly diagnosed CLL patients in order to analyze its association with clinical, laboratory, and molecular patients’ characteristics at diagnosis, as well as its prognostic relevance. MALAT1 was found to be upregulated in CLL patients in comparison to healthy controls, and expression levels were not related to age, leukocyte, lymphocyte and platelet count, serum β2-microglobulin, and IGHV somatic hypermutational status. On the other hand, high MALAT1 expression was associated with several favorable prognostic markers (high hemoglobin, low serum lactate dehydrogenase, earlier clinical stages, CD38-negative status), but also with unfavorable cytogenetics. Furthermore, an association between high MALAT1 levels and longer time to first treatment and overall survival in IGHV-unmutated CLL subtype was observed. In summary, our results imply that high MALAT1 expression at diagnosis may be a predictor of better prognosis and point to MALAT1 expression profiling as a candidate biomarker potentially useful in clinical practice.",
publisher = "MDPI",
journal = "International Journal of Molecular Sciences, International Journal of Molecular Sciences",
title = "Expression Pattern and Prognostic Significance of the Long Non-Coding RNA Metastasis-Associated Lung Adenocarcinoma Transcript 1 in Chronic Lymphocytic Leukemia",
number = "2",
pages = "922",
volume = "25",
doi = "10.3390/ijms25020922"
}

Tomić Vujović, K., Ugrin, M., Tošić, N., Vuković, V., Marjanović, I., Kostić, T., Stanković, S., Otašević, V., Šarac, S., Antić, D., Pavlović, S.,& Karan-Đurašević, T.. (2024). Expression Pattern and Prognostic Significance of the Long Non-Coding RNA Metastasis-Associated Lung Adenocarcinoma Transcript 1 in Chronic Lymphocytic Leukemia. in International Journal of Molecular Sciences
MDPI., 25(2), 922.
https://doi.org/10.3390/ijms25020922

Tomić Vujović K, Ugrin M, Tošić N, Vuković V, Marjanović I, Kostić T, Stanković S, Otašević V, Šarac S, Antić D, Pavlović S, Karan-Đurašević T. Expression Pattern and Prognostic Significance of the Long Non-Coding RNA Metastasis-Associated Lung Adenocarcinoma Transcript 1 in Chronic Lymphocytic Leukemia. in International Journal of Molecular Sciences. 2024;25(2):922.
doi:10.3390/ijms25020922 .

Tomić Vujović, Kristina, Ugrin, Milena, Tošić, Nataša, Vuković, Vojin, Marjanović, Irena, Kostić, Tatjana, Stanković, Sanja, Otašević, Vladimir, Šarac, Sofija, Antić, Darko, Pavlović, Sonja, Karan-Đurašević, Teodora, "Expression Pattern and Prognostic Significance of the Long Non-Coding RNA Metastasis-Associated Lung Adenocarcinoma Transcript 1 in Chronic Lymphocytic Leukemia" in International Journal of Molecular Sciences, 25, no. 2 (2024):922,
https://doi.org/10.3390/ijms25020922 . .

TY  - CONF
AU  - Gašić, Vladimir
AU  - Pravdić, Zlatko
AU  - Suvajdžić Vuković, Nada
AU  - Marjanović, Irena
AU  - Karan-Đurašević, Teodora
AU  - Pavlović, Sonja
AU  - Tošić, Nataša
PY  - 2023
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/1899
AB  - Acute myeloid leukemia (AML) is a malignancy of hematopoetic tissue which occurs due to a halt in
differentiation, loss of proliferation control and dysregulated apoptosis of myeloid progenitor cells. In
many cancers, as well as AML, dysregulation of apoptosis constitutes the basis of pathogenesis and this
phenomenon is important for chemotherapy success. Pharmacotranscriptomic markers of AML
prognosis could be targets of specific therapy. The anti-apoptotic gene BCL2 (B-cell lymphoma protein
2), the pro-apoptotic BAX (BCL2-associated X) and genes involved in drug resistance, like MDR1
could have a significant impact on AML prognosis and therapy response. Bone-marrow samples at
diagnosis were collected from 51 adult patients with AML-NK. Expressions of BCL2, BAX and MDR1
were analysed using the real-time polymerase chain reaction method. Statistical evaluation was
performed. The presence of chemoresistance was found to be associated with overexpression of BCL2
(BCL2+) (p=0.018), while underexpression of BAX in patients has shown a greater affinity towards
relapse (p=0.034). Evaluating the expressions of BCL2 and BAX in a combined effect has shown that
87% of patients with BAX/BCL2low status were resistant to therapy (p=0.024). BCL2+ status was
associated with high expression of MDR1 (p<0.001). Likewise, high expression of MDR1 was
associated with the absence of NPM1 and FLT3-ITD mutations (p=0.048 and p=0.010, respectively).
This is the first study that focused only on AML-NK patients, when it comes to analysis of BCL2, BAX
and MDR1 gene expression profiles. The results of this preliminary study have shown that high BCL2
expression would likely lead to resistance from chemotherapy, making anti-BCL2 treatment a viable
option in patients with this expression profile. A study on a larger group of patients could clarify the
prognostic importance of the studied genes in adult AML-NK patients and improve the precision
medicine approach in the field of hematology.
PB  - Sarajevo : Institute for Genetic Engineering and Biotechnology, University of Sarajevo
C3  - Genetics & Applications
T1  - Expression levels of BCL2, BAX and MDR1 as pharmacotranscriptomic and prognostic markers of prognosis in acute myeloid leukemia
VL  - 7
VL  - 2 (Special edition)
UR  - https://hdl.handle.net/21.15107/rcub_imagine_1899
ER  - 

@conference{
author = "Gašić, Vladimir and Pravdić, Zlatko and Suvajdžić Vuković, Nada and Marjanović, Irena and Karan-Đurašević, Teodora and Pavlović, Sonja and Tošić, Nataša",
year = "2023",
abstract = "Acute myeloid leukemia (AML) is a malignancy of hematopoetic tissue which occurs due to a halt in
differentiation, loss of proliferation control and dysregulated apoptosis of myeloid progenitor cells. In
many cancers, as well as AML, dysregulation of apoptosis constitutes the basis of pathogenesis and this
phenomenon is important for chemotherapy success. Pharmacotranscriptomic markers of AML
prognosis could be targets of specific therapy. The anti-apoptotic gene BCL2 (B-cell lymphoma protein
2), the pro-apoptotic BAX (BCL2-associated X) and genes involved in drug resistance, like MDR1
could have a significant impact on AML prognosis and therapy response. Bone-marrow samples at
diagnosis were collected from 51 adult patients with AML-NK. Expressions of BCL2, BAX and MDR1
were analysed using the real-time polymerase chain reaction method. Statistical evaluation was
performed. The presence of chemoresistance was found to be associated with overexpression of BCL2
(BCL2+) (p=0.018), while underexpression of BAX in patients has shown a greater affinity towards
relapse (p=0.034). Evaluating the expressions of BCL2 and BAX in a combined effect has shown that
87% of patients with BAX/BCL2low status were resistant to therapy (p=0.024). BCL2+ status was
associated with high expression of MDR1 (p<0.001). Likewise, high expression of MDR1 was
associated with the absence of NPM1 and FLT3-ITD mutations (p=0.048 and p=0.010, respectively).
This is the first study that focused only on AML-NK patients, when it comes to analysis of BCL2, BAX
and MDR1 gene expression profiles. The results of this preliminary study have shown that high BCL2
expression would likely lead to resistance from chemotherapy, making anti-BCL2 treatment a viable
option in patients with this expression profile. A study on a larger group of patients could clarify the
prognostic importance of the studied genes in adult AML-NK patients and improve the precision
medicine approach in the field of hematology.",
publisher = "Sarajevo : Institute for Genetic Engineering and Biotechnology, University of Sarajevo",
journal = "Genetics & Applications",
title = "Expression levels of BCL2, BAX and MDR1 as pharmacotranscriptomic and prognostic markers of prognosis in acute myeloid leukemia",
volume = "7, 2 (Special edition)",
url = "https://hdl.handle.net/21.15107/rcub_imagine_1899"
}

Gašić, V., Pravdić, Z., Suvajdžić Vuković, N., Marjanović, I., Karan-Đurašević, T., Pavlović, S.,& Tošić, N.. (2023). Expression levels of BCL2, BAX and MDR1 as pharmacotranscriptomic and prognostic markers of prognosis in acute myeloid leukemia. in Genetics & Applications
Sarajevo : Institute for Genetic Engineering and Biotechnology, University of Sarajevo., 7.
https://hdl.handle.net/21.15107/rcub_imagine_1899

Gašić V, Pravdić Z, Suvajdžić Vuković N, Marjanović I, Karan-Đurašević T, Pavlović S, Tošić N. Expression levels of BCL2, BAX and MDR1 as pharmacotranscriptomic and prognostic markers of prognosis in acute myeloid leukemia. in Genetics & Applications. 2023;7.
https://hdl.handle.net/21.15107/rcub_imagine_1899 .

Gašić, Vladimir, Pravdić, Zlatko, Suvajdžić Vuković, Nada, Marjanović, Irena, Karan-Đurašević, Teodora, Pavlović, Sonja, Tošić, Nataša, "Expression levels of BCL2, BAX and MDR1 as pharmacotranscriptomic and prognostic markers of prognosis in acute myeloid leukemia" in Genetics & Applications, 7 (2023),
https://hdl.handle.net/21.15107/rcub_imagine_1899 .

TY  - CONF
AU  - Tošić, Nataša
AU  - Ugrin, Milena
AU  - Vuković, Vojin
AU  - Marjanović, Irena
AU  - Kostić, Tatjana
AU  - Antić, Darko
AU  - Stanković, Sanja
AU  - Otašević, Vladimir
AU  - Tomić, Kristina
AU  - Šarac, Sofija
AU  - Mihaljević, Biljana
AU  - Pavlović, Sonja
AU  - Karan-Đurašević, Teodora
PY  - 2023
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/2118
AB  - Introduction: The long non-coding RNA (lncRNA) MALAT1 (metastasis-associated lung adenocarcinoma
transcript 1) dysregulated expression has been reported in a variety of cancers, but has been poorly investigated in chronic lymphocytic leukemia (CLL). The aim of thisstudy wasto investigate the expression
pattern of lncRNA MALAT1 in CLL, and evaluate its prognostic significance.
Methods: MALAT1 expression was analyzed in peripheral blood mononuclear cells of 114 newly-diagnosed CLL patients and 20 healthy controls by qRT-PCR, and association with clinical and biological features at diagnosis was assessed.
Results: MALAT1 was overexpressed in CLL compared to controlsamples(p<0.001). MALAT1 expression
was higher in male patients (p=0.003). It showed no correlation with age, leukocyte, lymphocyte and
platelet count, and serum β2-microglobulin, but exerted a positive correlation with hemoglobin level
(r=0.315, p=0.003) and a negative correlation with lactate dehydrogenase level (r=-0.303, p=0.004).
MALAT1 expression was higher in Binet A and B patients vs. Binet C patients (p=0.037). There was also a
trend toward higher MALAT1 expression in patients with favorable (del13q) and intermediate (normal
karyotype, trisomy12) cytogeneticsin comparison to patients with unfavorable (del11q and del17p) cytogenetics (p=0.059). In addition, high MALAT1 levels were associated with CD38-negative status
(p=0.017), but not with IGHV mutational status. While there was no association with the time to first
treatment, longer median overall survival in MALAT1 high- vs. MALAT1 low-expressing cases was observed (142 vs. 82 months, log rank p=0.032).
Conclusion: LncRNA MALAT1 is up-regulated in CLL. High MALAT1 expression at diagnosis may be associated with better prognosis.
PB  - Institute of Molecular Genetics and Genetic Engineering (IMGGE), University of Belgrade
C3  - CoMBoS2 – the Second Congress of Molecular Biologists of Serbia, Abstract Book – Trends in Molecular Biology, Special issue 06-08 October 2023, Belgrade, Serbia
T1  - Prognostic significance of the long non-coding rna malat1 expression in chronic lymphocytic leukemia
EP  - 60
SP  - 60
UR  - https://hdl.handle.net/21.15107/rcub_imagine_2118
ER  - 

@conference{
author = "Tošić, Nataša and Ugrin, Milena and Vuković, Vojin and Marjanović, Irena and Kostić, Tatjana and Antić, Darko and Stanković, Sanja and Otašević, Vladimir and Tomić, Kristina and Šarac, Sofija and Mihaljević, Biljana and Pavlović, Sonja and Karan-Đurašević, Teodora",
year = "2023",
abstract = "Introduction: The long non-coding RNA (lncRNA) MALAT1 (metastasis-associated lung adenocarcinoma
transcript 1) dysregulated expression has been reported in a variety of cancers, but has been poorly investigated in chronic lymphocytic leukemia (CLL). The aim of thisstudy wasto investigate the expression
pattern of lncRNA MALAT1 in CLL, and evaluate its prognostic significance.
Methods: MALAT1 expression was analyzed in peripheral blood mononuclear cells of 114 newly-diagnosed CLL patients and 20 healthy controls by qRT-PCR, and association with clinical and biological features at diagnosis was assessed.
Results: MALAT1 was overexpressed in CLL compared to controlsamples(p<0.001). MALAT1 expression
was higher in male patients (p=0.003). It showed no correlation with age, leukocyte, lymphocyte and
platelet count, and serum β2-microglobulin, but exerted a positive correlation with hemoglobin level
(r=0.315, p=0.003) and a negative correlation with lactate dehydrogenase level (r=-0.303, p=0.004).
MALAT1 expression was higher in Binet A and B patients vs. Binet C patients (p=0.037). There was also a
trend toward higher MALAT1 expression in patients with favorable (del13q) and intermediate (normal
karyotype, trisomy12) cytogeneticsin comparison to patients with unfavorable (del11q and del17p) cytogenetics (p=0.059). In addition, high MALAT1 levels were associated with CD38-negative status
(p=0.017), but not with IGHV mutational status. While there was no association with the time to first
treatment, longer median overall survival in MALAT1 high- vs. MALAT1 low-expressing cases was observed (142 vs. 82 months, log rank p=0.032).
Conclusion: LncRNA MALAT1 is up-regulated in CLL. High MALAT1 expression at diagnosis may be associated with better prognosis.",
publisher = "Institute of Molecular Genetics and Genetic Engineering (IMGGE), University of Belgrade",
journal = "CoMBoS2 – the Second Congress of Molecular Biologists of Serbia, Abstract Book – Trends in Molecular Biology, Special issue 06-08 October 2023, Belgrade, Serbia",
title = "Prognostic significance of the long non-coding rna malat1 expression in chronic lymphocytic leukemia",
pages = "60-60",
url = "https://hdl.handle.net/21.15107/rcub_imagine_2118"
}

Tošić, N., Ugrin, M., Vuković, V., Marjanović, I., Kostić, T., Antić, D., Stanković, S., Otašević, V., Tomić, K., Šarac, S., Mihaljević, B., Pavlović, S.,& Karan-Đurašević, T.. (2023). Prognostic significance of the long non-coding rna malat1 expression in chronic lymphocytic leukemia. in CoMBoS2 – the Second Congress of Molecular Biologists of Serbia, Abstract Book – Trends in Molecular Biology, Special issue 06-08 October 2023, Belgrade, Serbia
Institute of Molecular Genetics and Genetic Engineering (IMGGE), University of Belgrade., 60-60.
https://hdl.handle.net/21.15107/rcub_imagine_2118

Tošić N, Ugrin M, Vuković V, Marjanović I, Kostić T, Antić D, Stanković S, Otašević V, Tomić K, Šarac S, Mihaljević B, Pavlović S, Karan-Đurašević T. Prognostic significance of the long non-coding rna malat1 expression in chronic lymphocytic leukemia. in CoMBoS2 – the Second Congress of Molecular Biologists of Serbia, Abstract Book – Trends in Molecular Biology, Special issue 06-08 October 2023, Belgrade, Serbia. 2023;:60-60.
https://hdl.handle.net/21.15107/rcub_imagine_2118 .

Tošić, Nataša, Ugrin, Milena, Vuković, Vojin, Marjanović, Irena, Kostić, Tatjana, Antić, Darko, Stanković, Sanja, Otašević, Vladimir, Tomić, Kristina, Šarac, Sofija, Mihaljević, Biljana, Pavlović, Sonja, Karan-Đurašević, Teodora, "Prognostic significance of the long non-coding rna malat1 expression in chronic lymphocytic leukemia" in CoMBoS2 – the Second Congress of Molecular Biologists of Serbia, Abstract Book – Trends in Molecular Biology, Special issue 06-08 October 2023, Belgrade, Serbia (2023):60-60,
https://hdl.handle.net/21.15107/rcub_imagine_2118 .

TY  - JOUR
AU  - Denčić-Fekete, Marija
AU  - Terzić, Tatjana
AU  - Jaković, Ljubomir
AU  - Đurašinović, Vladislava
AU  - Karan-Đurašević, Teodora 
AU  - Radojković, Milica
AU  - Pavlović, Sonja
AU  - Bogdanović, Andrija
PY  - 2023
UR  - https://doiserbia.nb.rs/Article.aspx?ID=0042-84502200060D
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/2191
AB  - Introduction. The presence of aneuploidy in patients diagnosed with chronic lymphocytic leukemia (CLL), except trisomy 12, is considered quite uncommon. Hyperdiploidy or near-tetraploidy (occurring in 1–3% of all CLL patients) usually confer a poor prognosis. Case report. We report a patient in a progressive phase of CLL with near–triploid karyotype. The prognosis of the disease was more precisely determined by applying the cytogenetic analysis of the karyotype and was complemented with molecular methods and pathohistological examination. The complex karyotype was accompanied by the TP53, C-MYC, and IGH gene disruptions, the most probable cause of rapid evolution into Richter’s syndrome. Conclusion. The use of comprehensive contemporary diagnostic techniques is highly recommended in patients who are in the progressive phase of CLL, primarily for the adequate choice of management strategy. The presented case confirms that aneuploidy in CLL patients indicates poor prognosis, which is in accordance with previous publications reporting on cases of CLL patients with aneuploidy.
AB  - Uvod. Prisustvo aneuploidije kod bolesnika sa dijagnozom hronične limfocitne leukemije (HLL), sa izuzetkom trizomije 12, smatra se retkom pojavom. Pojava hiperdiploidnog ili kariotipa blizu tetraploidnog broja hromozoma (koji se javlja kod 1–3% svih bolesnika sa HLL) smatra se lošim prognostičkim parametrom. Prikaz bolesnika. Prikazan je bolesnik u uznapredovaloj fazi HLL sa kariotipom blizu triploidnog broja hromozoma. Prognoza bolesti je preciznije određena citogenetičkom analizom kariotipa bolesnika, i dopunjena molekularnim metodama i patohistološkom analizom. Otkriveno je prisustvo kompleksnog kariotipa udruženog sa poremećajima u genima TP53, C-MYC i IGH, što je najverovatnije bio uzrok brze progresije u Rihterov sindrom. Zaključak. Primena savremenih dijagnostičkih metoda veoma je značajna kod bolesnika u uznapredovaloj fazi HLL, prvenstveno zbog adekvatnog terapijskog pristupa. Prikazani slučaj ukazuje da je prisustvo aneuploidije kod bolesnika sa HLL loš prognostički znak, što je u saglasnosti sa prethodno publikovanim prikazima bolesnika sa HLL i sa aneuploidijom u kariotipu.
T2  - Vojnosanitetski pregled
T1  - Rapid progression to Richter’s syndrome in a patient with chronic lymphocytic leukemia and near-triploid karyotype
T1  - Brza progresija hronične limfocitne leukemije u Rihterov sindrom kod bolesnika sa kariotipom blizu triploidnog broja hromozom
EP  - 457
IS  - 5
SP  - 454
VL  - 80
DO  - 10.2298/VSP211111060D
ER  - 

@article{
author = "Denčić-Fekete, Marija and Terzić, Tatjana and Jaković, Ljubomir and Đurašinović, Vladislava and Karan-Đurašević, Teodora  and Radojković, Milica and Pavlović, Sonja and Bogdanović, Andrija",
year = "2023",
abstract = "Introduction. The presence of aneuploidy in patients diagnosed with chronic lymphocytic leukemia (CLL), except trisomy 12, is considered quite uncommon. Hyperdiploidy or near-tetraploidy (occurring in 1–3% of all CLL patients) usually confer a poor prognosis. Case report. We report a patient in a progressive phase of CLL with near–triploid karyotype. The prognosis of the disease was more precisely determined by applying the cytogenetic analysis of the karyotype and was complemented with molecular methods and pathohistological examination. The complex karyotype was accompanied by the TP53, C-MYC, and IGH gene disruptions, the most probable cause of rapid evolution into Richter’s syndrome. Conclusion. The use of comprehensive contemporary diagnostic techniques is highly recommended in patients who are in the progressive phase of CLL, primarily for the adequate choice of management strategy. The presented case confirms that aneuploidy in CLL patients indicates poor prognosis, which is in accordance with previous publications reporting on cases of CLL patients with aneuploidy., Uvod. Prisustvo aneuploidije kod bolesnika sa dijagnozom hronične limfocitne leukemije (HLL), sa izuzetkom trizomije 12, smatra se retkom pojavom. Pojava hiperdiploidnog ili kariotipa blizu tetraploidnog broja hromozoma (koji se javlja kod 1–3% svih bolesnika sa HLL) smatra se lošim prognostičkim parametrom. Prikaz bolesnika. Prikazan je bolesnik u uznapredovaloj fazi HLL sa kariotipom blizu triploidnog broja hromozoma. Prognoza bolesti je preciznije određena citogenetičkom analizom kariotipa bolesnika, i dopunjena molekularnim metodama i patohistološkom analizom. Otkriveno je prisustvo kompleksnog kariotipa udruženog sa poremećajima u genima TP53, C-MYC i IGH, što je najverovatnije bio uzrok brze progresije u Rihterov sindrom. Zaključak. Primena savremenih dijagnostičkih metoda veoma je značajna kod bolesnika u uznapredovaloj fazi HLL, prvenstveno zbog adekvatnog terapijskog pristupa. Prikazani slučaj ukazuje da je prisustvo aneuploidije kod bolesnika sa HLL loš prognostički znak, što je u saglasnosti sa prethodno publikovanim prikazima bolesnika sa HLL i sa aneuploidijom u kariotipu.",
journal = "Vojnosanitetski pregled",
title = "Rapid progression to Richter’s syndrome in a patient with chronic lymphocytic leukemia and near-triploid karyotype, Brza progresija hronične limfocitne leukemije u Rihterov sindrom kod bolesnika sa kariotipom blizu triploidnog broja hromozom",
pages = "457-454",
number = "5",
volume = "80",
doi = "10.2298/VSP211111060D"
}

Denčić-Fekete, M., Terzić, T., Jaković, L., Đurašinović, V., Karan-Đurašević, T., Radojković, M., Pavlović, S.,& Bogdanović, A.. (2023). Rapid progression to Richter’s syndrome in a patient with chronic lymphocytic leukemia and near-triploid karyotype. in Vojnosanitetski pregled, 80(5), 454-457.
https://doi.org/10.2298/VSP211111060D

Denčić-Fekete M, Terzić T, Jaković L, Đurašinović V, Karan-Đurašević T, Radojković M, Pavlović S, Bogdanović A. Rapid progression to Richter’s syndrome in a patient with chronic lymphocytic leukemia and near-triploid karyotype. in Vojnosanitetski pregled. 2023;80(5):454-457.
doi:10.2298/VSP211111060D .

Denčić-Fekete, Marija, Terzić, Tatjana, Jaković, Ljubomir, Đurašinović, Vladislava, Karan-Đurašević, Teodora , Radojković, Milica, Pavlović, Sonja, Bogdanović, Andrija, "Rapid progression to Richter’s syndrome in a patient with chronic lymphocytic leukemia and near-triploid karyotype" in Vojnosanitetski pregled, 80, no. 5 (2023):454-457,
https://doi.org/10.2298/VSP211111060D . .

TY  - CONF
AU  - Marjanović, Irena
AU  - Kraguljac Kurtović, Nada
AU  - Karan-Đurašević, Teodora
AU  - Pavlović, Sonja
AU  - Tošić, Nataša
PY  - 2023
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/2117
AB  - Introduction: CEBPA gene encodes a transciptional factor with an essential role in granulocyte differentiation process. In acute myeloid leukemia (AML), mutationsin CEBPA gene have been associated with
favorable outcome and up to now only the presence of double mutated CEBPA gene (CEBPAdm) was included in WHO classification. Prognostic influence of CEBPA mutationsin C-terminal (bZIP) region recently
have been proposed as a marker for better overalsurvival (OS), higher probability of achieving complete
remission (CR) and a lower risk of relapse. Since AML with normal karyotype (AML-NK) is a group with intermediate prognosis with the need for new prognostic markers, we analyzed the influence of bZIP CEBPA
mutations as an additional molecular marker in Serbian AML-NK patients.
Methods: CEBPA mutational screening was performed using a multiplex polymerase chain reaction–
based fragment length analysis. A total of 61 bone marrow samples were collected from de novo AMLNK patients.
Results: In our analysis, frequency of CEBPA mutations in Serbian AML-NK patients was 15% (12/61 patients). Six out of 12 patients had mutation in bZIP region (CEBPAbZIP+). All six CEBPAbZIP+ patients (100%)
achieved CR after induction chemotherapy versus 62% of CEBPAbZIP- patients. CEBPAbZIP+ patients showed a significantly longer OS (CEBPAbZIP+ 31.5 months vs CEBPAbZIP- 10 months) and disease free survival
(DFS) (CEBPAbZIP+ 30 months vs CEBPAbZIP- 10.5 months).
Conclusion: Our analysis of Serbian AML-NK patients showed CEBPAdm was not associated with better
prognosis but our results indicate that CEBPAbZIP+ status is a good candidate for a prognostic molecular
marker.
PB  - Institute of Molecular Genetics and Genetic Engineering (IMGGE), University of Belgrade
C3  - CoMBoS2 – the Second Congress of Molecular Biologists of Serbia, Abstract Book – Trends in Molecular Biology, Special issue 06-08 October 2023, Belgrade, Serbia
T1  - Prognostic significance of cebpa mutations in patients with normal-karyotype - acute myeloid leukemia
EP  - 58
SP  - 58
UR  - https://hdl.handle.net/21.15107/rcub_imagine_2117
ER  - 

@conference{
author = "Marjanović, Irena and Kraguljac Kurtović, Nada and Karan-Đurašević, Teodora and Pavlović, Sonja and Tošić, Nataša",
year = "2023",
abstract = "Introduction: CEBPA gene encodes a transciptional factor with an essential role in granulocyte differentiation process. In acute myeloid leukemia (AML), mutationsin CEBPA gene have been associated with
favorable outcome and up to now only the presence of double mutated CEBPA gene (CEBPAdm) was included in WHO classification. Prognostic influence of CEBPA mutationsin C-terminal (bZIP) region recently
have been proposed as a marker for better overalsurvival (OS), higher probability of achieving complete
remission (CR) and a lower risk of relapse. Since AML with normal karyotype (AML-NK) is a group with intermediate prognosis with the need for new prognostic markers, we analyzed the influence of bZIP CEBPA
mutations as an additional molecular marker in Serbian AML-NK patients.
Methods: CEBPA mutational screening was performed using a multiplex polymerase chain reaction–
based fragment length analysis. A total of 61 bone marrow samples were collected from de novo AMLNK patients.
Results: In our analysis, frequency of CEBPA mutations in Serbian AML-NK patients was 15% (12/61 patients). Six out of 12 patients had mutation in bZIP region (CEBPAbZIP+). All six CEBPAbZIP+ patients (100%)
achieved CR after induction chemotherapy versus 62% of CEBPAbZIP- patients. CEBPAbZIP+ patients showed a significantly longer OS (CEBPAbZIP+ 31.5 months vs CEBPAbZIP- 10 months) and disease free survival
(DFS) (CEBPAbZIP+ 30 months vs CEBPAbZIP- 10.5 months).
Conclusion: Our analysis of Serbian AML-NK patients showed CEBPAdm was not associated with better
prognosis but our results indicate that CEBPAbZIP+ status is a good candidate for a prognostic molecular
marker.",
publisher = "Institute of Molecular Genetics and Genetic Engineering (IMGGE), University of Belgrade",
journal = "CoMBoS2 – the Second Congress of Molecular Biologists of Serbia, Abstract Book – Trends in Molecular Biology, Special issue 06-08 October 2023, Belgrade, Serbia",
title = "Prognostic significance of cebpa mutations in patients with normal-karyotype - acute myeloid leukemia",
pages = "58-58",
url = "https://hdl.handle.net/21.15107/rcub_imagine_2117"
}

Marjanović, I., Kraguljac Kurtović, N., Karan-Đurašević, T., Pavlović, S.,& Tošić, N.. (2023). Prognostic significance of cebpa mutations in patients with normal-karyotype - acute myeloid leukemia. in CoMBoS2 – the Second Congress of Molecular Biologists of Serbia, Abstract Book – Trends in Molecular Biology, Special issue 06-08 October 2023, Belgrade, Serbia
Institute of Molecular Genetics and Genetic Engineering (IMGGE), University of Belgrade., 58-58.
https://hdl.handle.net/21.15107/rcub_imagine_2117

Marjanović I, Kraguljac Kurtović N, Karan-Đurašević T, Pavlović S, Tošić N. Prognostic significance of cebpa mutations in patients with normal-karyotype - acute myeloid leukemia. in CoMBoS2 – the Second Congress of Molecular Biologists of Serbia, Abstract Book – Trends in Molecular Biology, Special issue 06-08 October 2023, Belgrade, Serbia. 2023;:58-58.
https://hdl.handle.net/21.15107/rcub_imagine_2117 .

Marjanović, Irena, Kraguljac Kurtović, Nada, Karan-Đurašević, Teodora, Pavlović, Sonja, Tošić, Nataša, "Prognostic significance of cebpa mutations in patients with normal-karyotype - acute myeloid leukemia" in CoMBoS2 – the Second Congress of Molecular Biologists of Serbia, Abstract Book – Trends in Molecular Biology, Special issue 06-08 October 2023, Belgrade, Serbia (2023):58-58,
https://hdl.handle.net/21.15107/rcub_imagine_2117 .

TY  - CHAP
AU  - Karan-Đurašević, Teodora
PY  - 2023
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/2247
AB  - Opsežne imunogenetičke studije sprovedene tokom proteklih nekoliko decenija u oblasti hronične limfocitne
leukemije (HLL) su identifikovale grupe pacijenata koji eksprimiraju visoko homologne, skoro identične
imunoglobulinske molekule koji ulaze u sastav B-ćelijskog receptora (BĆR IG). Ovaj fenomen, nazvan
„BĆR stereotipija“, obuhvata oko 30% HLL i predstavlja najvažniju potvrdu uloge antigenske stimulacije u
patogenezi i evoluciji bolesti. Na osnovu sekvence CDR3 regiona teških lanaca IG definisani su stereotipni
subsetovi koji ispoljavaju konzistentne subset-specifične biološke i kliničke karakteristike. Neki od najzastupljenijih
subsetova imaju i jasan prognostički značaj, tako da se čak mogu smatrati različitim varijantama
bolesti. Subklasifikacija HLL bazirana na BĆR stereotipiji je omogućila kompartmentalizovan pristup u istraživanju
ove bolesti, i otvorila mogućnost za precizniju stratifikaciju pacijenata, kao i uspešniju prognostiku
i lečenje, uprkos izrazitoj kliničkoj heterogenosti HLL.
AB  - During the past several decades, extensive immunogenetic research of chronic lymphocytic leukemia
(CLL) led to the identification of groups of patients expressing highly homologous, almost identical B-cell
receptor immunoglobulin molecules (BCR IG). This phenomenon, termed „BCR stereotypy“, accounts for
around 30% of all CLL and represents the strongest evidence for the role of antigenic stimulation in CLL
pathogenesis and evolution. Based on the sequence of CDR3 region within IG heavy chains multiple stereotyped
subsets have been defined, which display consistent subset-specific biological and clinical characteristics.
Some of the most frequent subsets also exert strong prognostic significance and can be
considered to be distinct disease variants. Stereotypy-based CLL subclassification enabled compartmentalized
approach in the research of this disease, and offered the possibility of refining stratification of patients
that can improve prognostication and clinical decision-making despite extreme heterogeneity of
CLL.
PB  - Beograd : Institut za molekularnu genetiku i genetičko inženjerstvo
T2  - Trendovi u molekularnoj Biologiji
T1  - Stereotipija B-ćelijskog receptora u hroničnoj limfocitnoj leukemiji
T1  - B-cell receptor stereotypy in chronic lymphocytic leukemia
EP  - 77
IS  - 3
SP  - 58
UR  - https://hdl.handle.net/21.15107/rcub_imagine_2247
ER  - 

@inbook{
author = "Karan-Đurašević, Teodora",
year = "2023",
abstract = "Opsežne imunogenetičke studije sprovedene tokom proteklih nekoliko decenija u oblasti hronične limfocitne
leukemije (HLL) su identifikovale grupe pacijenata koji eksprimiraju visoko homologne, skoro identične
imunoglobulinske molekule koji ulaze u sastav B-ćelijskog receptora (BĆR IG). Ovaj fenomen, nazvan
„BĆR stereotipija“, obuhvata oko 30% HLL i predstavlja najvažniju potvrdu uloge antigenske stimulacije u
patogenezi i evoluciji bolesti. Na osnovu sekvence CDR3 regiona teških lanaca IG definisani su stereotipni
subsetovi koji ispoljavaju konzistentne subset-specifične biološke i kliničke karakteristike. Neki od najzastupljenijih
subsetova imaju i jasan prognostički značaj, tako da se čak mogu smatrati različitim varijantama
bolesti. Subklasifikacija HLL bazirana na BĆR stereotipiji je omogućila kompartmentalizovan pristup u istraživanju
ove bolesti, i otvorila mogućnost za precizniju stratifikaciju pacijenata, kao i uspešniju prognostiku
i lečenje, uprkos izrazitoj kliničkoj heterogenosti HLL., During the past several decades, extensive immunogenetic research of chronic lymphocytic leukemia
(CLL) led to the identification of groups of patients expressing highly homologous, almost identical B-cell
receptor immunoglobulin molecules (BCR IG). This phenomenon, termed „BCR stereotypy“, accounts for
around 30% of all CLL and represents the strongest evidence for the role of antigenic stimulation in CLL
pathogenesis and evolution. Based on the sequence of CDR3 region within IG heavy chains multiple stereotyped
subsets have been defined, which display consistent subset-specific biological and clinical characteristics.
Some of the most frequent subsets also exert strong prognostic significance and can be
considered to be distinct disease variants. Stereotypy-based CLL subclassification enabled compartmentalized
approach in the research of this disease, and offered the possibility of refining stratification of patients
that can improve prognostication and clinical decision-making despite extreme heterogeneity of
CLL.",
publisher = "Beograd : Institut za molekularnu genetiku i genetičko inženjerstvo",
journal = "Trendovi u molekularnoj Biologiji",
booktitle = "Stereotipija B-ćelijskog receptora u hroničnoj limfocitnoj leukemiji, B-cell receptor stereotypy in chronic lymphocytic leukemia",
pages = "77-58",
number = "3",
url = "https://hdl.handle.net/21.15107/rcub_imagine_2247"
}

Karan-Đurašević, T.. (2023). Stereotipija B-ćelijskog receptora u hroničnoj limfocitnoj leukemiji. in Trendovi u molekularnoj Biologiji
Beograd : Institut za molekularnu genetiku i genetičko inženjerstvo.(3), 58-77.
https://hdl.handle.net/21.15107/rcub_imagine_2247

Karan-Đurašević T. Stereotipija B-ćelijskog receptora u hroničnoj limfocitnoj leukemiji. in Trendovi u molekularnoj Biologiji. 2023;(3):58-77.
https://hdl.handle.net/21.15107/rcub_imagine_2247 .

Karan-Đurašević, Teodora, "Stereotipija B-ćelijskog receptora u hroničnoj limfocitnoj leukemiji" in Trendovi u molekularnoj Biologiji, no. 3 (2023):58-77,
https://hdl.handle.net/21.15107/rcub_imagine_2247 .

TY  - CONF
AU  - Karan-Đurašević, Teodora
AU  - Kaćanski, Nataša
AU  - Kostić, Tatjana
AU  - Marjanović, Irena
AU  - Tošić, Nataša
AU  - Perić, Jelena
AU  - Kolarović, Jovanka
AU  - Janić, Dragana
AU  - Pavlović, Sonja
PY  - 2023
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/2113
AB  - Introduction: Childhood B-cell precursor acute lymphoblastic leukemic (BCP-ALL) can be traced back to
birth using leukemic clone-specific immunoglobulin heavy chain (IGH) rearrangements, implying prenatal origin of this disease. The aim of this study was to analyze neonatal blood spots (Guthrie cards) of
childhood BCP-ALL patients for the presence of clonotypic IGH rearrangements.
Methods: The study enrolled 24 patients aged 1 to 9.6 years. Based on the sequences of IGH rearrangements identified in diagnostic lymphoblasts, 2 patient-specific primers were designed for each patient
and used in semi-nested PCR for the detection of preleukemic clones at birth.
Results: Clonotypic IGH rearrangements were detected in neonatal blood spots of 54.2% of patients. In
two cases that had double IGH rearrangements at diagnosis, only one rearrangement was present at
birth, while in the third case both leukemic rearrangements were detected in neonatal blood. Guthrie
card-positive findings were significantly more frequent in children ≤5 years of age than in older children
(p=0.011). Regarding patients’characteristics at birth and at diagnosis, Guthrie card-positivity was not associated with sex, birth weight and mother’s age, as well as with white blood cell count, percentage of
bone marrow blasts, immunophenotype and the presence of ETV6/RUNX1 and TCF3/PBX1 fusion genes
at diagnosis.
Conclusion: Our study confirms that a large proportion of childhood BCP-ALL originates in utero, regardless of the molecularsubtype defined by chromosomal aberrations. The latency period to the overt
leukemia depends on the presence of preleukemic clone at birth, as well as on the postnatal transforming genetic events.
PB  - Institute of Molecular Genetics and Genetic Engineering (IMGGE), University of Belgrade
C3  - CoMBoS2 – the Second Congress of Molecular Biologists of Serbia, Abstract Book – Trends in Molecular Biology, Special issue 06-08 October 2023, Belgrade, Serbia
T1  - Detection of preleukemic clones in neonatal blood spots of children with B-cell precursor acute lymphoblastic leukemia
EP  - 59
SP  - 59
UR  - https://hdl.handle.net/21.15107/rcub_imagine_2113
ER  - 

@conference{
author = "Karan-Đurašević, Teodora and Kaćanski, Nataša and Kostić, Tatjana and Marjanović, Irena and Tošić, Nataša and Perić, Jelena and Kolarović, Jovanka and Janić, Dragana and Pavlović, Sonja",
year = "2023",
abstract = "Introduction: Childhood B-cell precursor acute lymphoblastic leukemic (BCP-ALL) can be traced back to
birth using leukemic clone-specific immunoglobulin heavy chain (IGH) rearrangements, implying prenatal origin of this disease. The aim of this study was to analyze neonatal blood spots (Guthrie cards) of
childhood BCP-ALL patients for the presence of clonotypic IGH rearrangements.
Methods: The study enrolled 24 patients aged 1 to 9.6 years. Based on the sequences of IGH rearrangements identified in diagnostic lymphoblasts, 2 patient-specific primers were designed for each patient
and used in semi-nested PCR for the detection of preleukemic clones at birth.
Results: Clonotypic IGH rearrangements were detected in neonatal blood spots of 54.2% of patients. In
two cases that had double IGH rearrangements at diagnosis, only one rearrangement was present at
birth, while in the third case both leukemic rearrangements were detected in neonatal blood. Guthrie
card-positive findings were significantly more frequent in children ≤5 years of age than in older children
(p=0.011). Regarding patients’characteristics at birth and at diagnosis, Guthrie card-positivity was not associated with sex, birth weight and mother’s age, as well as with white blood cell count, percentage of
bone marrow blasts, immunophenotype and the presence of ETV6/RUNX1 and TCF3/PBX1 fusion genes
at diagnosis.
Conclusion: Our study confirms that a large proportion of childhood BCP-ALL originates in utero, regardless of the molecularsubtype defined by chromosomal aberrations. The latency period to the overt
leukemia depends on the presence of preleukemic clone at birth, as well as on the postnatal transforming genetic events.",
publisher = "Institute of Molecular Genetics and Genetic Engineering (IMGGE), University of Belgrade",
journal = "CoMBoS2 – the Second Congress of Molecular Biologists of Serbia, Abstract Book – Trends in Molecular Biology, Special issue 06-08 October 2023, Belgrade, Serbia",
title = "Detection of preleukemic clones in neonatal blood spots of children with B-cell precursor acute lymphoblastic leukemia",
pages = "59-59",
url = "https://hdl.handle.net/21.15107/rcub_imagine_2113"
}

Karan-Đurašević, T., Kaćanski, N., Kostić, T., Marjanović, I., Tošić, N., Perić, J., Kolarović, J., Janić, D.,& Pavlović, S.. (2023). Detection of preleukemic clones in neonatal blood spots of children with B-cell precursor acute lymphoblastic leukemia. in CoMBoS2 – the Second Congress of Molecular Biologists of Serbia, Abstract Book – Trends in Molecular Biology, Special issue 06-08 October 2023, Belgrade, Serbia
Institute of Molecular Genetics and Genetic Engineering (IMGGE), University of Belgrade., 59-59.
https://hdl.handle.net/21.15107/rcub_imagine_2113

Karan-Đurašević T, Kaćanski N, Kostić T, Marjanović I, Tošić N, Perić J, Kolarović J, Janić D, Pavlović S. Detection of preleukemic clones in neonatal blood spots of children with B-cell precursor acute lymphoblastic leukemia. in CoMBoS2 – the Second Congress of Molecular Biologists of Serbia, Abstract Book – Trends in Molecular Biology, Special issue 06-08 October 2023, Belgrade, Serbia. 2023;:59-59.
https://hdl.handle.net/21.15107/rcub_imagine_2113 .

Karan-Đurašević, Teodora, Kaćanski, Nataša, Kostić, Tatjana, Marjanović, Irena, Tošić, Nataša, Perić, Jelena, Kolarović, Jovanka, Janić, Dragana, Pavlović, Sonja, "Detection of preleukemic clones in neonatal blood spots of children with B-cell precursor acute lymphoblastic leukemia" in CoMBoS2 – the Second Congress of Molecular Biologists of Serbia, Abstract Book – Trends in Molecular Biology, Special issue 06-08 October 2023, Belgrade, Serbia (2023):59-59,
https://hdl.handle.net/21.15107/rcub_imagine_2113 .

TY  - JOUR
AU  - Čolović, Nataša
AU  - Đorđević, Vesna
AU  - Radojković, Milica
AU  - Karan-Đurašević, Teodora
AU  - Tošić, Nataša
PY  - 2023
UR  - https://doiserbia.nb.rs/Article.aspx?ID=0370-81792300100C
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/2292
AB  - Introduction. Chromosomal numerical aberrations are very common in hematological malignancies, but near-tetraploidy (80-104 chromosomes) is rare in myeloid lineage malignancies, with only a few cases reported in myelodysplastic syndrome (MDS). Due to a small number of cases with this rare cytogenetic abnormality, clinicopathological significance of near-tetraploidy in MDS is still unknown. In this case report we present a case of de novo MDS patient with near-tetraploidy in association with TP53 mutation, and we aimed to elucidate the prognostic significance of this rare genetic feature. Case Outline. In August of 2018 a 71-year-old male presented with severe anemia, thrombocytopenia, and leucopenia and enlarged spleen. Laboratory data were as follows: hemoglobin (Hb) 93 g/L, white blood cells (WBC) 2.8×109/L and platelets 23x109/L. The bone marrow aspirate was hypercellular, megakaryocytes were not found, granulocytic cells were 15% with signs of dysplasia, with 16% of blast cells without Auer rods. The finding was in correlation with diagnosis of MDS, type RAEB2 which was also confirmed by immunophenotyping. Cytogenetic finding was near-tetraploidy (48,XY+mar[10]/92,XXYY[10]), and TP53 mutational analysis showed the presence of mutation in exon 8 (p.D281A; c.842 A>C). The patient received from time-to-time packed red blood cells and platelets, and died four months after initial diagnosis. Conclusion. Near-tetraploidy associated with TP53 mutation has been described only in few MDS cases. Results of these reports including ours suggest that the association of TP53 mutation and near-tetra polyploidy is a poor prognostic factor.
AB  - Нумеричке аберације хромозома су веома честе код хематолошких малигнитета, али су приближне тетраплои- дије (80–104 хромозома) ретке у малигнитетима мијелоидне лозе, са само неколико случајева пријављених у мијелоди- спластичком синдрому (МДС). Због малог броја случајева са овом ретком цитогенетском абнормалношћу, клиничко- -патолошки значај приближне тетраплоидије у МДС-у је још увек непознат. Овим приказом de novo болесника са МДС-ом, са приближном тетраплоидијом и мутацијом у гену TP53, циљ нам је био да расветлимо прогностички значај ове рет- ке генетске карактеристикe. Приказ болесника Приказан је 71-годишњи болесник који је у августу 2018. године развио симптоме тешке анемије, тромбоцитопеније, леукопеније и увећане слезине. Лабо- раторијске анализе су показале следеће: хемоглобин 93 g/L, леукоцити 2,8 × 109 /L и тромбоцити 23 × 109 /L. Аспират коштане сржи је био хиперћелијски, мегакариоцити нису на- ђени, 15% гранулоцитa је било са знацима дисплазије, 16% бластa без Ауерових штапића. Налаз је одговарао дијагнози МДС-а, типа рефракторне анемије са вишком бласта 2, што је потврђено и имунолошком фенотипизацијом. Цитогенет- ском анализом утврђено је присуство приближне тетрапло- идије (48,XY+mar10/92,XXYY[10]), а анализа мутација у гену TP53 показала је присуство мутације у егзону 8 (p.D281A; c.842 A > C). Болесник је по потреби примао трансфузију еритроцита и тромбоците, а умро је четири месеца након почетне дијагнозе. Закључак Присуство приближне тетраплоидије удружене са мутацијама у гену TP53 описано је само у неколико слу- чајева МДС-а. Резултати ових случајева, као и наши резул- тати, указују на то да приближна тетраплоидија повезана са присуством мутација у гену TP53 представља фактор лоше прогнозе.
T2  - Srpski arhiv za celokupno lekarstvo
T1  - Rare case of myelodysplastic syndrome with near-tetraploidy and TP53 mutation
T1  - Мијелодиспластични синдром са приближном тетраплоидијом удруженом са мутацијом гена TP53 – редак случај
EP  - n/a
IS  - n/a
SP  - n/a
DO  - 10.2298/SARH230728100C
ER  - 

@article{
author = "Čolović, Nataša and Đorđević, Vesna and Radojković, Milica and Karan-Đurašević, Teodora and Tošić, Nataša",
year = "2023",
abstract = "Introduction. Chromosomal numerical aberrations are very common in hematological malignancies, but near-tetraploidy (80-104 chromosomes) is rare in myeloid lineage malignancies, with only a few cases reported in myelodysplastic syndrome (MDS). Due to a small number of cases with this rare cytogenetic abnormality, clinicopathological significance of near-tetraploidy in MDS is still unknown. In this case report we present a case of de novo MDS patient with near-tetraploidy in association with TP53 mutation, and we aimed to elucidate the prognostic significance of this rare genetic feature. Case Outline. In August of 2018 a 71-year-old male presented with severe anemia, thrombocytopenia, and leucopenia and enlarged spleen. Laboratory data were as follows: hemoglobin (Hb) 93 g/L, white blood cells (WBC) 2.8×109/L and platelets 23x109/L. The bone marrow aspirate was hypercellular, megakaryocytes were not found, granulocytic cells were 15% with signs of dysplasia, with 16% of blast cells without Auer rods. The finding was in correlation with diagnosis of MDS, type RAEB2 which was also confirmed by immunophenotyping. Cytogenetic finding was near-tetraploidy (48,XY+mar[10]/92,XXYY[10]), and TP53 mutational analysis showed the presence of mutation in exon 8 (p.D281A; c.842 A>C). The patient received from time-to-time packed red blood cells and platelets, and died four months after initial diagnosis. Conclusion. Near-tetraploidy associated with TP53 mutation has been described only in few MDS cases. Results of these reports including ours suggest that the association of TP53 mutation and near-tetra polyploidy is a poor prognostic factor., Нумеричке аберације хромозома су веома честе код хематолошких малигнитета, али су приближне тетраплои- дије (80–104 хромозома) ретке у малигнитетима мијелоидне лозе, са само неколико случајева пријављених у мијелоди- спластичком синдрому (МДС). Због малог броја случајева са овом ретком цитогенетском абнормалношћу, клиничко- -патолошки значај приближне тетраплоидије у МДС-у је још увек непознат. Овим приказом de novo болесника са МДС-ом, са приближном тетраплоидијом и мутацијом у гену TP53, циљ нам је био да расветлимо прогностички значај ове рет- ке генетске карактеристикe. Приказ болесника Приказан је 71-годишњи болесник који је у августу 2018. године развио симптоме тешке анемије, тромбоцитопеније, леукопеније и увећане слезине. Лабо- раторијске анализе су показале следеће: хемоглобин 93 g/L, леукоцити 2,8 × 109 /L и тромбоцити 23 × 109 /L. Аспират коштане сржи је био хиперћелијски, мегакариоцити нису на- ђени, 15% гранулоцитa је било са знацима дисплазије, 16% бластa без Ауерових штапића. Налаз је одговарао дијагнози МДС-а, типа рефракторне анемије са вишком бласта 2, што је потврђено и имунолошком фенотипизацијом. Цитогенет- ском анализом утврђено је присуство приближне тетрапло- идије (48,XY+mar10/92,XXYY[10]), а анализа мутација у гену TP53 показала је присуство мутације у егзону 8 (p.D281A; c.842 A > C). Болесник је по потреби примао трансфузију еритроцита и тромбоците, а умро је четири месеца након почетне дијагнозе. Закључак Присуство приближне тетраплоидије удружене са мутацијама у гену TP53 описано је само у неколико слу- чајева МДС-а. Резултати ових случајева, као и наши резул- тати, указују на то да приближна тетраплоидија повезана са присуством мутација у гену TP53 представља фактор лоше прогнозе.",
journal = "Srpski arhiv za celokupno lekarstvo",
title = "Rare case of myelodysplastic syndrome with near-tetraploidy and TP53 mutation, Мијелодиспластични синдром са приближном тетраплоидијом удруженом са мутацијом гена TP53 – редак случај",
pages = "n/a-n/a",
number = "n/a",
doi = "10.2298/SARH230728100C"
}

Čolović, N., Đorđević, V., Radojković, M., Karan-Đurašević, T.,& Tošić, N.. (2023). Rare case of myelodysplastic syndrome with near-tetraploidy and TP53 mutation. in Srpski arhiv za celokupno lekarstvo(n/a), n/a-n/a.
https://doi.org/10.2298/SARH230728100C

Čolović N, Đorđević V, Radojković M, Karan-Đurašević T, Tošić N. Rare case of myelodysplastic syndrome with near-tetraploidy and TP53 mutation. in Srpski arhiv za celokupno lekarstvo. 2023;(n/a):n/a-n/a.
doi:10.2298/SARH230728100C .

Čolović, Nataša, Đorđević, Vesna, Radojković, Milica, Karan-Đurašević, Teodora, Tošić, Nataša, "Rare case of myelodysplastic syndrome with near-tetraploidy and TP53 mutation" in Srpski arhiv za celokupno lekarstvo, no. n/a (2023):n/a-n/a,
https://doi.org/10.2298/SARH230728100C . .

TY  - JOUR
AU  - Pravdić, Zlatko
AU  - Vuković, Nada Suvajdžić
AU  - Gašić, Vladimir
AU  - Marjanović, Irena
AU  - Karan-Đurašević, Teodora
AU  - Pavlović, Sonja
AU  - Tošić, Nataša
PY  - 2023
UR  - https://sciendo.com/article/10.2478/raon-2023-0017
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/2291
AB  - Background: Deregulation of the apoptotic process underlies the pathogenesis of many cancers, including leukemia, but is also very important for the success of chemotherapy treatment. Therefore, the gene expression profile of main apoptotic factors, such as anti-apoptotic BCL2 (B-cell lymphoma protein 2) and pro-apoptotic BAX (BCL2-associated X), as well as genes involved in the multi-drug resistance (ABCB1), could have significant impact on the prognosis and could be used as targets for specific therapy.Patients and methodsWe analyzed the expression of BCL2, BAX, and ABCB1 in bone-marrow samples collected at diagnosis from 51 adult patients with acute myeloid leukemia with normal karyotype (AML-NK) using real-time polymerase chain reaction method, and examined their prognostic potential.ResultsIncreased expression of BCL2 (BCL2+) was associated with the presence of chemoresistance (p = 0.024), while patients with low BAX expression were more prone to relapse (p = 0.047). Analysis of the combined effect of BCL2 and BAX expression showed that 87% of patients with BAX/BCL2low status were resistant to therapy (p = 0.044). High expression of ABCB1 was associated with BCL2+ status (p < 0.001), and with absence FLT3-ITD mutations (p = 0.019).ConclusionsThe present analysis of BCL2, BAX, and ABCB1 gene expression profiles is the first study focusing solely
PB  - Sciendo
T2  - Radiology and Oncology
T1  - The influence of BCL2, BAX, and ABCB1 gene expression on prognosis of adult de novo acute myeloid leukemia with normal karyotype patients
EP  - 248
IS  - 2
SP  - 239
VL  - 57
DO  - 10.2478/raon-2023-0017
ER  - 

@article{
author = "Pravdić, Zlatko and Vuković, Nada Suvajdžić and Gašić, Vladimir and Marjanović, Irena and Karan-Đurašević, Teodora and Pavlović, Sonja and Tošić, Nataša",
year = "2023",
abstract = "Background: Deregulation of the apoptotic process underlies the pathogenesis of many cancers, including leukemia, but is also very important for the success of chemotherapy treatment. Therefore, the gene expression profile of main apoptotic factors, such as anti-apoptotic BCL2 (B-cell lymphoma protein 2) and pro-apoptotic BAX (BCL2-associated X), as well as genes involved in the multi-drug resistance (ABCB1), could have significant impact on the prognosis and could be used as targets for specific therapy.Patients and methodsWe analyzed the expression of BCL2, BAX, and ABCB1 in bone-marrow samples collected at diagnosis from 51 adult patients with acute myeloid leukemia with normal karyotype (AML-NK) using real-time polymerase chain reaction method, and examined their prognostic potential.ResultsIncreased expression of BCL2 (BCL2+) was associated with the presence of chemoresistance (p = 0.024), while patients with low BAX expression were more prone to relapse (p = 0.047). Analysis of the combined effect of BCL2 and BAX expression showed that 87% of patients with BAX/BCL2low status were resistant to therapy (p = 0.044). High expression of ABCB1 was associated with BCL2+ status (p < 0.001), and with absence FLT3-ITD mutations (p = 0.019).ConclusionsThe present analysis of BCL2, BAX, and ABCB1 gene expression profiles is the first study focusing solely",
publisher = "Sciendo",
journal = "Radiology and Oncology",
title = "The influence of BCL2, BAX, and ABCB1 gene expression on prognosis of adult de novo acute myeloid leukemia with normal karyotype patients",
pages = "248-239",
number = "2",
volume = "57",
doi = "10.2478/raon-2023-0017"
}

Pravdić, Z., Vuković, N. S., Gašić, V., Marjanović, I., Karan-Đurašević, T., Pavlović, S.,& Tošić, N.. (2023). The influence of BCL2, BAX, and ABCB1 gene expression on prognosis of adult de novo acute myeloid leukemia with normal karyotype patients. in Radiology and Oncology
Sciendo., 57(2), 239-248.
https://doi.org/10.2478/raon-2023-0017

Pravdić Z, Vuković NS, Gašić V, Marjanović I, Karan-Đurašević T, Pavlović S, Tošić N. The influence of BCL2, BAX, and ABCB1 gene expression on prognosis of adult de novo acute myeloid leukemia with normal karyotype patients. in Radiology and Oncology. 2023;57(2):239-248.
doi:10.2478/raon-2023-0017 .

Pravdić, Zlatko, Vuković, Nada Suvajdžić, Gašić, Vladimir, Marjanović, Irena, Karan-Đurašević, Teodora, Pavlović, Sonja, Tošić, Nataša, "The influence of BCL2, BAX, and ABCB1 gene expression on prognosis of adult de novo acute myeloid leukemia with normal karyotype patients" in Radiology and Oncology, 57, no. 2 (2023):239-248,
https://doi.org/10.2478/raon-2023-0017 . .

TY  - CONF
AU  - Denčić Fekete, Marija
AU  - Karan-Đurašević, Teodora
AU  - Vuković, Vojin
AU  - Jovanović, Jelica
AU  - Sanader, Senka
AU  - Antić, Darko
PY  - 2023
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/2102
AB  - Chronic lymphocyti c leukemia (CLL) is a malignancy of mature CD5+ B lymphocytes that is characterized by excepti onal
clinical and biological heterogeneity. The Rai and Binet staging systems, developed in the late 1970s to early 1980s,
are used in clinical practi ce to strati fy CLL pati ents into risk categories and to help guide clinical follow-up opti ons: to
treat or to watch and wait. However, in early-stage disease, these systems are unable to predict what pati ents will
face the progression to a more aggressive disease. That means, a number of molecular markers with prognosti c and/
or predicti ve impact exist and their assessment is strongly recommended in all pati ents prior to treatment initi ati on.
One of the fi rst recognized prognosti c genomic aberrati ons in CLL include those detected by fl uorescence in situ
hybridizati on (FISH): del(17p), del(11q), trisomy 12 and del(13q), and the immunoglobulin heavy variable (IGHV) gene
somati c hypermutati on (SHM) status. Moreover, the rapid development of genomics techniques greatly expanded
the understanding of CLL at the molecular level in the past decade. This resulted in the discovery of many newer
prognosti c markers based on chromosomal aberrati ons or gene mutati ons. For instance, next-generati on sequencing
(NGS) studies have led to the discovery of recurrently mutated genes in CLL, such as NOTCH1, SF3B1, BIRC3, XPO1,
POT1, NFKBIE and EGR2, that are associated with poor clinical outcome. Among all of these biomarkers, the disti ncti on
between markers of prognosti c and predicti ve values should be made. Prognosti c markers refer to biomarkers that can
provide informati on regarding the pati ent's outcome regardless of treatment. They are o����� en assessed before treatment
to help guide decisions on to treat or not. Markers associated with overall survival (OS) or ti me to fi rst treatment
(TTFT) represent such examples. On the other hand, predicti ve markers are related to therapeuti c interventi ons
with the ability to predict treatment response to a drug. These markers are normally assessed when pati ents receive
the parti cular therapy. Some markers can be both prognosti c and predicti ve. The Nati onal Comprehensive Cancer
Network guideline recommends testi ng of TP53 geneti c alterati ons, IGHV mutati on status, and several well-established
cytogeneti c markers for CLL prognosti cati on. Of these, TP53 mutati ons, IGHV unmutated status, del(17p), and
del(11q), as well as complex karyotype (the presence of three or more unrelated clonal chromosomal abnormaliti es
in a sample), are associated with poor prognosis. Normal karyotype and trisomy 12 are considered as intermediate
prognosti c factors, whereas del(13q) is associated with a favorable prognosis. The higher frequencies of the
previously menti oned unfavorable markers (except for IGHV) found in the treated populati on usually imply the clonal
evoluti on during disease progression or change in clonal dynamics induced by therapies, especially chemotherapies.
Diff erent molecular and genomic techniques are employed for detecti ng molecular biomarkers in CLL. For IGHV
mutati on status, the preferred method is Sanger sequencing to detect mutati ons in genomic DNA or cDNA following
PCR, and align the resulti ng sequences to the germline IGHV using the IMGT/V-QUEST analyti c tool, where ≥ 98%
homology to the germ line is interpreted as unmutated, >2% nonhomology as mutated, and 97.0% to 97.9% is
interpreted as borderline. Prognosti cally signifi cant chromosomal abnormaliti es are frequently detected using
fl uorescence in situ hybridizati on, array comparati ve genomic hybridizati on or conventi onal karyotyping. Fluorescence
in situ hybridizati on, although off ers a high sensiti vity and specifi city, requires prior knowledge of chromosomal
lesions for the probe designs and are limited to the chosen panel genes. The technique has limitati ons in detecti ng
possible complex cytogeneti c abnormaliti es, as well. On the other hand, karyotyping and array comparati ve genomic
hybridizati on provide genome-wide coverage. Despite the fact that array comparati ve genomic hybridizati on does not
eff ecti vely detect balanced chromosomal rearrangements, it uncovers more genomic abnormaliti es than karyotyping
as the probe-based technology examines the chromosomal structure at a much higher resoluti on. Development in
NGS technology in the past two decades, made the technique, especially targeted sequencing of gene panels, much
less costly and accessible. Currently, in Serbia, geneti c techniques such as FISH, conventi onal karyotyping, Sanger
sequencing and NGS are available for detecti on of CLL biomarkers. Advances in the understanding of CLL pathogenesis
have consequently led to the development of several highly eff ecti ve targeted therapies, including Bruton tyrosine
kinase (BTK), phosphati dylinositol 3-kinase, and BCL2 apoptosis regulator (BCL2) directed inhibitors. B-cell survival
and proliferati on is regulated by the BCR signaling pathway. In normal B cells, BCR is triggered by anti gen ligati on,
leading to acti vati on of a cascade of tyrosine kinases, including BTK. BCR signaling is aberrantly acti vated in many B-cell
malignancies, including CLL. Ibruti nib has demonstrated high clinical effi cacy acti ng as an irreversible potent inhibitor of
Bruton's tyrosine kinase and targets several key components of the BCR pathway. However, despite having 80% to 90%
response rate, 10% to 15% of CLL pati ents, who respond initi ally, develop ibruti nib resistance and disease relapse in 2 to
3 years on ibruti nib treatment, mainly because of the acquisiti on of a BTK C481S mutati on. The mutati on prevents the
drug from forming a covalent bond with the C481 residue that weakened the drug-BTK binding by 500-fold. As a result,
BCR signaling and cell proliferati on were restored in the tumor cells. BTK mutati ons may be found in approximately 70%
of CLL pati ents who progressed on ibruti nib treatment. Another resistance mechanism is through acquired acti vati ng
mutati ons in PLCG2, which is found in approximately 10% of the cases. Given these evidences, the current Nati onal
Comprehensive Cancer Network guideline recommends testi ng for BTK and PLCG2 mutati ons for CLL pati ents receiving
ibruti nib who are suspected of having disease progression. NGS has become the opti mal method for detecti ng BTK
or PLCG2 mutati ons in the se����� ng of ibruti nib treatment, as multi ple mutati ons in both genes may occur in the same
specimen. Currently, approximately 20% of CLL pati ents who progressed on ibruti nib do not have either BTK or PLCG2
mutati ons; thus, with NGS, it is possible to uncover other less common but yet undefi ned drug-resistance mutati ons.
In additi on to BTK and PLCG2 mutati ons known to confer ibruti nib resistance, other molecular markers have
been associated with an upfront high risk of relapse on ibruti nib treatment. It has been reported that complex
karyotype, del(17p)/TP53 mutati on, and del(18p) at baseline before ibruti nib treatment are strongly associated
with disease relapse. Other approved targeted agents for CLL treatment include the phosphati dylinositol 3-kinase
inhibitors idelalisib and duvelisib and BCL2 inhibitor venetoclax. For venetoclax, a novel BCL2-G101V mutati on was
identi fi ed to prevent drug acti vity through drug-protein interacti on. Each pati ent with CLL may have several clinical
and molecular markers of confl icti ng prognosti c signifi cance simultaneously, making the precise prognosti cati on
challenging. Today is of the greatest importance to apply ultrasensiti ve techniques to reveal molecular relapses
a����� er therapy initi ati on and to detect minimal residual disease a����� er pati ents achieve complete responses.
PB  - Belgrade :  Serbian Association on for Cancer Research
C3  - 6th Congress of the Serbian Association for Cancer Research (SDIR)
T1  - Signifi cance of molecular diagnosti cs in therapy of chronic lymphocytic leukemia
EP  - 55
IS  - 1
SP  - 54
UR  - https://hdl.handle.net/21.15107/rcub_imagine_2102
ER  - 

@conference{
author = "Denčić Fekete, Marija and Karan-Đurašević, Teodora and Vuković, Vojin and Jovanović, Jelica and Sanader, Senka and Antić, Darko",
year = "2023",
abstract = "Chronic lymphocyti c leukemia (CLL) is a malignancy of mature CD5+ B lymphocytes that is characterized by excepti onal
clinical and biological heterogeneity. The Rai and Binet staging systems, developed in the late 1970s to early 1980s,
are used in clinical practi ce to strati fy CLL pati ents into risk categories and to help guide clinical follow-up opti ons: to
treat or to watch and wait. However, in early-stage disease, these systems are unable to predict what pati ents will
face the progression to a more aggressive disease. That means, a number of molecular markers with prognosti c and/
or predicti ve impact exist and their assessment is strongly recommended in all pati ents prior to treatment initi ati on.
One of the fi rst recognized prognosti c genomic aberrati ons in CLL include those detected by fl uorescence in situ
hybridizati on (FISH): del(17p), del(11q), trisomy 12 and del(13q), and the immunoglobulin heavy variable (IGHV) gene
somati c hypermutati on (SHM) status. Moreover, the rapid development of genomics techniques greatly expanded
the understanding of CLL at the molecular level in the past decade. This resulted in the discovery of many newer
prognosti c markers based on chromosomal aberrati ons or gene mutati ons. For instance, next-generati on sequencing
(NGS) studies have led to the discovery of recurrently mutated genes in CLL, such as NOTCH1, SF3B1, BIRC3, XPO1,
POT1, NFKBIE and EGR2, that are associated with poor clinical outcome. Among all of these biomarkers, the disti ncti on
between markers of prognosti c and predicti ve values should be made. Prognosti c markers refer to biomarkers that can
provide informati on regarding the pati ent's outcome regardless of treatment. They are o����� en assessed before treatment
to help guide decisions on to treat or not. Markers associated with overall survival (OS) or ti me to fi rst treatment
(TTFT) represent such examples. On the other hand, predicti ve markers are related to therapeuti c interventi ons
with the ability to predict treatment response to a drug. These markers are normally assessed when pati ents receive
the parti cular therapy. Some markers can be both prognosti c and predicti ve. The Nati onal Comprehensive Cancer
Network guideline recommends testi ng of TP53 geneti c alterati ons, IGHV mutati on status, and several well-established
cytogeneti c markers for CLL prognosti cati on. Of these, TP53 mutati ons, IGHV unmutated status, del(17p), and
del(11q), as well as complex karyotype (the presence of three or more unrelated clonal chromosomal abnormaliti es
in a sample), are associated with poor prognosis. Normal karyotype and trisomy 12 are considered as intermediate
prognosti c factors, whereas del(13q) is associated with a favorable prognosis. The higher frequencies of the
previously menti oned unfavorable markers (except for IGHV) found in the treated populati on usually imply the clonal
evoluti on during disease progression or change in clonal dynamics induced by therapies, especially chemotherapies.
Diff erent molecular and genomic techniques are employed for detecti ng molecular biomarkers in CLL. For IGHV
mutati on status, the preferred method is Sanger sequencing to detect mutati ons in genomic DNA or cDNA following
PCR, and align the resulti ng sequences to the germline IGHV using the IMGT/V-QUEST analyti c tool, where ≥ 98%
homology to the germ line is interpreted as unmutated, >2% nonhomology as mutated, and 97.0% to 97.9% is
interpreted as borderline. Prognosti cally signifi cant chromosomal abnormaliti es are frequently detected using
fl uorescence in situ hybridizati on, array comparati ve genomic hybridizati on or conventi onal karyotyping. Fluorescence
in situ hybridizati on, although off ers a high sensiti vity and specifi city, requires prior knowledge of chromosomal
lesions for the probe designs and are limited to the chosen panel genes. The technique has limitati ons in detecti ng
possible complex cytogeneti c abnormaliti es, as well. On the other hand, karyotyping and array comparati ve genomic
hybridizati on provide genome-wide coverage. Despite the fact that array comparati ve genomic hybridizati on does not
eff ecti vely detect balanced chromosomal rearrangements, it uncovers more genomic abnormaliti es than karyotyping
as the probe-based technology examines the chromosomal structure at a much higher resoluti on. Development in
NGS technology in the past two decades, made the technique, especially targeted sequencing of gene panels, much
less costly and accessible. Currently, in Serbia, geneti c techniques such as FISH, conventi onal karyotyping, Sanger
sequencing and NGS are available for detecti on of CLL biomarkers. Advances in the understanding of CLL pathogenesis
have consequently led to the development of several highly eff ecti ve targeted therapies, including Bruton tyrosine
kinase (BTK), phosphati dylinositol 3-kinase, and BCL2 apoptosis regulator (BCL2) directed inhibitors. B-cell survival
and proliferati on is regulated by the BCR signaling pathway. In normal B cells, BCR is triggered by anti gen ligati on,
leading to acti vati on of a cascade of tyrosine kinases, including BTK. BCR signaling is aberrantly acti vated in many B-cell
malignancies, including CLL. Ibruti nib has demonstrated high clinical effi cacy acti ng as an irreversible potent inhibitor of
Bruton's tyrosine kinase and targets several key components of the BCR pathway. However, despite having 80% to 90%
response rate, 10% to 15% of CLL pati ents, who respond initi ally, develop ibruti nib resistance and disease relapse in 2 to
3 years on ibruti nib treatment, mainly because of the acquisiti on of a BTK C481S mutati on. The mutati on prevents the
drug from forming a covalent bond with the C481 residue that weakened the drug-BTK binding by 500-fold. As a result,
BCR signaling and cell proliferati on were restored in the tumor cells. BTK mutati ons may be found in approximately 70%
of CLL pati ents who progressed on ibruti nib treatment. Another resistance mechanism is through acquired acti vati ng
mutati ons in PLCG2, which is found in approximately 10% of the cases. Given these evidences, the current Nati onal
Comprehensive Cancer Network guideline recommends testi ng for BTK and PLCG2 mutati ons for CLL pati ents receiving
ibruti nib who are suspected of having disease progression. NGS has become the opti mal method for detecti ng BTK
or PLCG2 mutati ons in the se����� ng of ibruti nib treatment, as multi ple mutati ons in both genes may occur in the same
specimen. Currently, approximately 20% of CLL pati ents who progressed on ibruti nib do not have either BTK or PLCG2
mutati ons; thus, with NGS, it is possible to uncover other less common but yet undefi ned drug-resistance mutati ons.
In additi on to BTK and PLCG2 mutati ons known to confer ibruti nib resistance, other molecular markers have
been associated with an upfront high risk of relapse on ibruti nib treatment. It has been reported that complex
karyotype, del(17p)/TP53 mutati on, and del(18p) at baseline before ibruti nib treatment are strongly associated
with disease relapse. Other approved targeted agents for CLL treatment include the phosphati dylinositol 3-kinase
inhibitors idelalisib and duvelisib and BCL2 inhibitor venetoclax. For venetoclax, a novel BCL2-G101V mutati on was
identi fi ed to prevent drug acti vity through drug-protein interacti on. Each pati ent with CLL may have several clinical
and molecular markers of confl icti ng prognosti c signifi cance simultaneously, making the precise prognosti cati on
challenging. Today is of the greatest importance to apply ultrasensiti ve techniques to reveal molecular relapses
a����� er therapy initi ati on and to detect minimal residual disease a����� er pati ents achieve complete responses.",
publisher = "Belgrade :  Serbian Association on for Cancer Research",
journal = "6th Congress of the Serbian Association for Cancer Research (SDIR)",
title = "Signifi cance of molecular diagnosti cs in therapy of chronic lymphocytic leukemia",
pages = "55-54",
number = "1",
url = "https://hdl.handle.net/21.15107/rcub_imagine_2102"
}

Denčić Fekete, M., Karan-Đurašević, T., Vuković, V., Jovanović, J., Sanader, S.,& Antić, D.. (2023). Signifi cance of molecular diagnosti cs in therapy of chronic lymphocytic leukemia. in 6th Congress of the Serbian Association for Cancer Research (SDIR)
Belgrade :  Serbian Association on for Cancer Research.(1), 54-55.
https://hdl.handle.net/21.15107/rcub_imagine_2102

Denčić Fekete M, Karan-Đurašević T, Vuković V, Jovanović J, Sanader S, Antić D. Signifi cance of molecular diagnosti cs in therapy of chronic lymphocytic leukemia. in 6th Congress of the Serbian Association for Cancer Research (SDIR). 2023;(1):54-55.
https://hdl.handle.net/21.15107/rcub_imagine_2102 .

Denčić Fekete, Marija, Karan-Đurašević, Teodora, Vuković, Vojin, Jovanović, Jelica, Sanader, Senka, Antić, Darko, "Signifi cance of molecular diagnosti cs in therapy of chronic lymphocytic leukemia" in 6th Congress of the Serbian Association for Cancer Research (SDIR), no. 1 (2023):54-55,
https://hdl.handle.net/21.15107/rcub_imagine_2102 .

TY  - CONF
AU  - Karan-Đurašević, Teodora
AU  - Ugrin, Milena
AU  - Vuković, Vojin
AU  - Antić, Darko
AU  - Stanković, Sanja
AU  - Marjanović, Irena
AU  - Kostić, Tatjana
AU  - Otasević, Vladimir
AU  - Tomić, Kristina
AU  - Sarać, Sofija
AU  - Mihaljević, Biljana
AU  - Pavlović, Sonja
AU  - Tošić, Nataša
PY  - 2023
UR  - https://journals.lww.com/hemasphere/fulltext/2023/08003/pb1917__expression_of_the_long_non_coding_rna.1797.aspx
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/2155
AB  - Background: The long non-coding RNA (lncRNA) MALAT1 (metastasis-associated lung adenocarcinoma transcript 1) dysregulated expression and prognostic significance have been reported in a variety of cancers, including hematological malignancies, but have been poorly investigated in chronic lymphocytic leukemia (CLL). Acting through regulation of gene expression at transcriptional and post-transcriptional level, lncRNA MALAT1 is involved in many cellular processes such as proliferation, apoptosis, migration and drug resistance. However, its role as either an oncogene or a tumor-supressor is still controversial, and clearly tumor type-dependent.  Aims: To analyze the expression pattern of lncRNA MALAT1 in CLL, and evaluate its prognostic relevance.  Methods: This study enrolled 114 unselected CLL patients (pts) and 20 healthy controls (hcs). Clinical and laboratory characteristics of pts were determined at diagnosis, while genetic analyses were performed during the period prior to first treatment. The expression of MALAT1 was analyzed in peripheral blood mononuclear cells by RQ-PCR, using TaqMan chemistry and GAPDH as endogenous control; relative quantification was made by comparative ddCt method, using hcs as calibrator.  Results: CLL cohort consisted of 81 males and 33 females (male/female=2.45), with median age at diagnosis of 59 years (range 33-80). Hcs group consisted of 15 males and 5 females (male/female=3), with median age at diagnosis of 71 years (range 65-85). Distribution of Binet stages (112/114 pts) was as follows: A-46.4%, B-39.3%, C-14.3%. Del13q, normal karyotype, trisomy12, del11q and del17p were detected by FISH in 33%, 35%, 9.3%, 10.3% and 12.4% of pts, respectively (97/114 pts). CD38 status (85/114 pts) was negative in 70.6% and positive in 29.4% of pts. Regarding IGHV mutational status (114 pts), 41.2% of pts were mutated, and 58.8% unmutated. Median follow-up was 72 months (range 1-360). LncRNA MALAT1 was overexpressed in CLL pts compared to hcs (p<0.001). Median value of MALAT1 expression was used to divide the cohort into MALAT1low and MALAT1high groups, and association with clinical and biological features at diagnosis was assessed. In both pts and hcs MALAT1 expression was not associated with age but, unlike hcs, MALAT1high status was significantly associated with male sex in CLL (p=0.003). Regarding laboratory parameters, MALAT1 expression showed no correlation with leukocyte, lymphocyte and platelet counts, and serum β2-microglobulin, but exerted a positive correlation with hemoglobin level (r=0.315, p=0.003) and a negative correlation with lactate dehydrogenase (LDH) level (r=-0.303, p=0.004). MALAT1 expression was higher in Binet A and B pts vs. Binet C pts (p=0.037). There was also a trend toward higher MALAT1 expression in pts with favorable (del13q) and intermediate (normal karyotype, trisomy12) cytogenetics in comparison to pts with unfavorable (del11q and del17p) cytogenetics (p=0.059). In addition, MALAT1high status was associated with CD38-negative status (p=0.017), but not with IGHV mutational status. Finally, while the association of MALAT1 expression with the time to first treatment was not detected, longer median overall survival (OS) in MALAT1high vs. MALAT1low group was observed (142 vs. 82 months, log rank p=0.032).  Summary/Conclusion: LncRNA MALAT1 is up-regulated in CLL. However, high MALAT1 expression is associated with several favorable prognostic markers (high hemoglobin, low LDH, early clinical stages, negative CD38 status), as well as longer OS. The exact mechanisms of MALAT1 function in CLL pathogenesis and/or progression remain to be determined.
C3  - HemaSphere
T1  - PB1917: EXPRESSION OF THE LONG NON-CODING RNA MALAT1 IN CHRONIC LYMPHOCYTIC LEUKEMIA
IS  - S3
SP  - e1785725
VL  - 7
DO  - 10.1097/01.HS9.0000974492.17857.25
ER  - 

@conference{
author = "Karan-Đurašević, Teodora and Ugrin, Milena and Vuković, Vojin and Antić, Darko and Stanković, Sanja and Marjanović, Irena and Kostić, Tatjana and Otasević, Vladimir and Tomić, Kristina and Sarać, Sofija and Mihaljević, Biljana and Pavlović, Sonja and Tošić, Nataša",
year = "2023",
abstract = "Background: The long non-coding RNA (lncRNA) MALAT1 (metastasis-associated lung adenocarcinoma transcript 1) dysregulated expression and prognostic significance have been reported in a variety of cancers, including hematological malignancies, but have been poorly investigated in chronic lymphocytic leukemia (CLL). Acting through regulation of gene expression at transcriptional and post-transcriptional level, lncRNA MALAT1 is involved in many cellular processes such as proliferation, apoptosis, migration and drug resistance. However, its role as either an oncogene or a tumor-supressor is still controversial, and clearly tumor type-dependent.  Aims: To analyze the expression pattern of lncRNA MALAT1 in CLL, and evaluate its prognostic relevance.  Methods: This study enrolled 114 unselected CLL patients (pts) and 20 healthy controls (hcs). Clinical and laboratory characteristics of pts were determined at diagnosis, while genetic analyses were performed during the period prior to first treatment. The expression of MALAT1 was analyzed in peripheral blood mononuclear cells by RQ-PCR, using TaqMan chemistry and GAPDH as endogenous control; relative quantification was made by comparative ddCt method, using hcs as calibrator.  Results: CLL cohort consisted of 81 males and 33 females (male/female=2.45), with median age at diagnosis of 59 years (range 33-80). Hcs group consisted of 15 males and 5 females (male/female=3), with median age at diagnosis of 71 years (range 65-85). Distribution of Binet stages (112/114 pts) was as follows: A-46.4%, B-39.3%, C-14.3%. Del13q, normal karyotype, trisomy12, del11q and del17p were detected by FISH in 33%, 35%, 9.3%, 10.3% and 12.4% of pts, respectively (97/114 pts). CD38 status (85/114 pts) was negative in 70.6% and positive in 29.4% of pts. Regarding IGHV mutational status (114 pts), 41.2% of pts were mutated, and 58.8% unmutated. Median follow-up was 72 months (range 1-360). LncRNA MALAT1 was overexpressed in CLL pts compared to hcs (p<0.001). Median value of MALAT1 expression was used to divide the cohort into MALAT1low and MALAT1high groups, and association with clinical and biological features at diagnosis was assessed. In both pts and hcs MALAT1 expression was not associated with age but, unlike hcs, MALAT1high status was significantly associated with male sex in CLL (p=0.003). Regarding laboratory parameters, MALAT1 expression showed no correlation with leukocyte, lymphocyte and platelet counts, and serum β2-microglobulin, but exerted a positive correlation with hemoglobin level (r=0.315, p=0.003) and a negative correlation with lactate dehydrogenase (LDH) level (r=-0.303, p=0.004). MALAT1 expression was higher in Binet A and B pts vs. Binet C pts (p=0.037). There was also a trend toward higher MALAT1 expression in pts with favorable (del13q) and intermediate (normal karyotype, trisomy12) cytogenetics in comparison to pts with unfavorable (del11q and del17p) cytogenetics (p=0.059). In addition, MALAT1high status was associated with CD38-negative status (p=0.017), but not with IGHV mutational status. Finally, while the association of MALAT1 expression with the time to first treatment was not detected, longer median overall survival (OS) in MALAT1high vs. MALAT1low group was observed (142 vs. 82 months, log rank p=0.032).  Summary/Conclusion: LncRNA MALAT1 is up-regulated in CLL. However, high MALAT1 expression is associated with several favorable prognostic markers (high hemoglobin, low LDH, early clinical stages, negative CD38 status), as well as longer OS. The exact mechanisms of MALAT1 function in CLL pathogenesis and/or progression remain to be determined.",
journal = "HemaSphere",
title = "PB1917: EXPRESSION OF THE LONG NON-CODING RNA MALAT1 IN CHRONIC LYMPHOCYTIC LEUKEMIA",
number = "S3",
pages = "e1785725",
volume = "7",
doi = "10.1097/01.HS9.0000974492.17857.25"
}

Karan-Đurašević, T., Ugrin, M., Vuković, V., Antić, D., Stanković, S., Marjanović, I., Kostić, T., Otasević, V., Tomić, K., Sarać, S., Mihaljević, B., Pavlović, S.,& Tošić, N.. (2023). PB1917: EXPRESSION OF THE LONG NON-CODING RNA MALAT1 IN CHRONIC LYMPHOCYTIC LEUKEMIA. in HemaSphere, 7(S3), e1785725.
https://doi.org/10.1097/01.HS9.0000974492.17857.25

Karan-Đurašević T, Ugrin M, Vuković V, Antić D, Stanković S, Marjanović I, Kostić T, Otasević V, Tomić K, Sarać S, Mihaljević B, Pavlović S, Tošić N. PB1917: EXPRESSION OF THE LONG NON-CODING RNA MALAT1 IN CHRONIC LYMPHOCYTIC LEUKEMIA. in HemaSphere. 2023;7(S3):e1785725.
doi:10.1097/01.HS9.0000974492.17857.25 .

Karan-Đurašević, Teodora, Ugrin, Milena, Vuković, Vojin, Antić, Darko, Stanković, Sanja, Marjanović, Irena, Kostić, Tatjana, Otasević, Vladimir, Tomić, Kristina, Sarać, Sofija, Mihaljević, Biljana, Pavlović, Sonja, Tošić, Nataša, "PB1917: EXPRESSION OF THE LONG NON-CODING RNA MALAT1 IN CHRONIC LYMPHOCYTIC LEUKEMIA" in HemaSphere, 7, no. S3 (2023):e1785725,
https://doi.org/10.1097/01.HS9.0000974492.17857.25 . .

TY  - JOUR
AU  - Kačanski, Nataša
AU  - Kolarović, Jovanka
AU  - Kostić, Tatjana
AU  - Marjanović, Irena
AU  - Janić, Dragana
AU  - Pavlović, Sonja
AU  - Karan-Đurašević, Teodora
PY  - 2023
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/2213
AB  - Introduction
Childhood B-cell precursor acute lymphoblastic leukemia (BCP-ALL) can be traced back to birth using leukemic clone-specific immunoglobulin heavy chain (IGH) rearrangements, implying prenatal origin of this disease.

Methods
We retrospectively analyzed neonatal blood spots (Guthrie cards) of 24 patients with childhood BCP-ALL aged 1–9.6 years (median 3.1 years) for the presence of clonotypic IGH rearrangements identified in diagnostic bone marrow samples. Based on the sequences of IGH rearrangements, 2 patient-specific primers were designed for each patient and used in semi-nested polymerase chain reaction for the detection of preleukemic clones at birth.

Results
Clonotypic IGH rearrangements were detected in neonatal blood spots of 54.2% of patients (13/24). In two cases with double IGH rearrangements detected at diagnosis, only one rearrangement was present at birth, while in the third case both leukemic rearrangements were detected in neonatal blood. Guthrie card-positive findings were significantly more frequent in children ≤5 years of age than in older children (p = 0.011). Regarding patients' characteristics at birth and at diagnosis, Guthrie card-positivity was not associated with sex, birth weight and mother's age, as well as with white blood cell count, percentage of bone marrow blasts, immunophenotype and the presence of ETV6/RUNX1 and TCF3/PBX1 fusion genes at diagnosis.

Conclusion
Our study confirms that a large proportion of childhood BCP-ALL originates in utero, regardless of the molecular subtype defined by chromosomal aberrations. The observed trend toward younger age at diagnosis in Guthrie card-positive versus Guthrie card-negative patients implies that the age at diagnosis depends on the presence of preleukemic clone at birth, as well as on the timing of postnatal transforming genetic events.
PB  - John Wiley & Sons Ltd
T2  - International Journal of Laboratory Hematology
T1  - Presence of leukemic clone-specific immunoglobulin heavy chain rearrangements in neonatal blood spots of children with B-cell precursor acute lymphoblastic leukemia
IS  - 6
VL  - 45
DO  - doi.org/10.1111/ijlh.14200
ER  - 

@article{
author = "Kačanski, Nataša and Kolarović, Jovanka and Kostić, Tatjana and Marjanović, Irena and Janić, Dragana and Pavlović, Sonja and Karan-Đurašević, Teodora",
year = "2023",
abstract = "Introduction
Childhood B-cell precursor acute lymphoblastic leukemia (BCP-ALL) can be traced back to birth using leukemic clone-specific immunoglobulin heavy chain (IGH) rearrangements, implying prenatal origin of this disease.

Methods
We retrospectively analyzed neonatal blood spots (Guthrie cards) of 24 patients with childhood BCP-ALL aged 1–9.6 years (median 3.1 years) for the presence of clonotypic IGH rearrangements identified in diagnostic bone marrow samples. Based on the sequences of IGH rearrangements, 2 patient-specific primers were designed for each patient and used in semi-nested polymerase chain reaction for the detection of preleukemic clones at birth.

Results
Clonotypic IGH rearrangements were detected in neonatal blood spots of 54.2% of patients (13/24). In two cases with double IGH rearrangements detected at diagnosis, only one rearrangement was present at birth, while in the third case both leukemic rearrangements were detected in neonatal blood. Guthrie card-positive findings were significantly more frequent in children ≤5 years of age than in older children (p = 0.011). Regarding patients' characteristics at birth and at diagnosis, Guthrie card-positivity was not associated with sex, birth weight and mother's age, as well as with white blood cell count, percentage of bone marrow blasts, immunophenotype and the presence of ETV6/RUNX1 and TCF3/PBX1 fusion genes at diagnosis.

Conclusion
Our study confirms that a large proportion of childhood BCP-ALL originates in utero, regardless of the molecular subtype defined by chromosomal aberrations. The observed trend toward younger age at diagnosis in Guthrie card-positive versus Guthrie card-negative patients implies that the age at diagnosis depends on the presence of preleukemic clone at birth, as well as on the timing of postnatal transforming genetic events.",
publisher = "John Wiley & Sons Ltd",
journal = "International Journal of Laboratory Hematology",
title = "Presence of leukemic clone-specific immunoglobulin heavy chain rearrangements in neonatal blood spots of children with B-cell precursor acute lymphoblastic leukemia",
number = "6",
volume = "45",
doi = "doi.org/10.1111/ijlh.14200"
}

Kačanski, N., Kolarović, J., Kostić, T., Marjanović, I., Janić, D., Pavlović, S.,& Karan-Đurašević, T.. (2023). Presence of leukemic clone-specific immunoglobulin heavy chain rearrangements in neonatal blood spots of children with B-cell precursor acute lymphoblastic leukemia. in International Journal of Laboratory Hematology
John Wiley & Sons Ltd., 45(6).
https://doi.org/doi.org/10.1111/ijlh.14200

Kačanski N, Kolarović J, Kostić T, Marjanović I, Janić D, Pavlović S, Karan-Đurašević T. Presence of leukemic clone-specific immunoglobulin heavy chain rearrangements in neonatal blood spots of children with B-cell precursor acute lymphoblastic leukemia. in International Journal of Laboratory Hematology. 2023;45(6).
doi:doi.org/10.1111/ijlh.14200 .

Kačanski, Nataša, Kolarović, Jovanka, Kostić, Tatjana, Marjanović, Irena, Janić, Dragana, Pavlović, Sonja, Karan-Đurašević, Teodora, "Presence of leukemic clone-specific immunoglobulin heavy chain rearrangements in neonatal blood spots of children with B-cell precursor acute lymphoblastic leukemia" in International Journal of Laboratory Hematology, 45, no. 6 (2023),
https://doi.org/doi.org/10.1111/ijlh.14200 . .

TY  - JOUR
AU  - Tošić, Nataša
AU  - Ugrin, Milena
AU  - Marjanović, Irena
AU  - Kostić, Tatjana
AU  - Vuković, Vojin
AU  - Tomić, Kristina
AU  - Otasević, Vladimir
AU  - Antić, Darko
AU  - Mihaljević, Biljana
AU  - Pavlović, Sonja
AU  - Karan-Đurašević, Teodora
PY  - 2023
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/1510
AB  - Introduction The B-cell lymphoma/leukaemia 11A (BCL11A) gene encodes a Kruppel-like transcription factor involved in lymphocyte development during normal haematopoiesis. Aberrant expression of BCL11A has been observed in several haematological malignancies, including chronic lymphocytic leukaemia (CLL). However, its functions in the regulatory networks of malignant B lymphocytes are poorly understood, as are the relations to clinical course and outcome of B-cell malignancies, particularly CLL. Methods The expression of BCL11A was analysed in peripheral blood mononuclear cells of 87 newly-diagnosed CLL patients by quantitative reverse-transcriptase polymerase chain reaction (qRT-PCR), and association with clinical and molecular variables was assessed. Results BCL11A was significantly overexpressed in CLL samples compared to control samples (p  lt  0.001). BCL11A expression level exhibited no association with age, sex, leukocyte, lymphocyte and platelet counts, haemoglobin level, serum beta 2-microglobulin, CD38 status and cytogenetic abnormalities. On the other hand, high BCL11A expression was associated with low serum lactate dehydrogenase (p = 0.031), Binet A stage (p = 0.047) and mutated IGHV (p = 0.028). In addition, a positive correlation with BCL2/BAX mRNA ratio was observed (r = 0.36; p  lt  0.001). Regarding the association with the time to first treatment (TTFT), a trend towards longer median TTFT in BCL11A high- versus BCL11A low-expressing cases was detected (21 vs. 6 months; p = 0.164). Conclusion The results of this study show that BCL11A is upregulated in CLL patients, and that high BCL11A expression at diagnosis may be associated with better prognosis. These data are consistent with the role of BCL11A expression in CLL biology, and imply its potential prognostic relevance.
PB  - Wiley, Hoboken
T2  - International Journal of Laboratory Hematology
T1  - Expression of BCL11A in chronic lymphocytic leukaemia
EP  - 71
IS  - 1
SP  - 64
VL  - 45
DO  - 10.1111/ijlh.13969
ER  - 

@article{
author = "Tošić, Nataša and Ugrin, Milena and Marjanović, Irena and Kostić, Tatjana and Vuković, Vojin and Tomić, Kristina and Otasević, Vladimir and Antić, Darko and Mihaljević, Biljana and Pavlović, Sonja and Karan-Đurašević, Teodora",
year = "2023",
abstract = "Introduction The B-cell lymphoma/leukaemia 11A (BCL11A) gene encodes a Kruppel-like transcription factor involved in lymphocyte development during normal haematopoiesis. Aberrant expression of BCL11A has been observed in several haematological malignancies, including chronic lymphocytic leukaemia (CLL). However, its functions in the regulatory networks of malignant B lymphocytes are poorly understood, as are the relations to clinical course and outcome of B-cell malignancies, particularly CLL. Methods The expression of BCL11A was analysed in peripheral blood mononuclear cells of 87 newly-diagnosed CLL patients by quantitative reverse-transcriptase polymerase chain reaction (qRT-PCR), and association with clinical and molecular variables was assessed. Results BCL11A was significantly overexpressed in CLL samples compared to control samples (p  lt  0.001). BCL11A expression level exhibited no association with age, sex, leukocyte, lymphocyte and platelet counts, haemoglobin level, serum beta 2-microglobulin, CD38 status and cytogenetic abnormalities. On the other hand, high BCL11A expression was associated with low serum lactate dehydrogenase (p = 0.031), Binet A stage (p = 0.047) and mutated IGHV (p = 0.028). In addition, a positive correlation with BCL2/BAX mRNA ratio was observed (r = 0.36; p  lt  0.001). Regarding the association with the time to first treatment (TTFT), a trend towards longer median TTFT in BCL11A high- versus BCL11A low-expressing cases was detected (21 vs. 6 months; p = 0.164). Conclusion The results of this study show that BCL11A is upregulated in CLL patients, and that high BCL11A expression at diagnosis may be associated with better prognosis. These data are consistent with the role of BCL11A expression in CLL biology, and imply its potential prognostic relevance.",
publisher = "Wiley, Hoboken",
journal = "International Journal of Laboratory Hematology",
title = "Expression of BCL11A in chronic lymphocytic leukaemia",
pages = "71-64",
number = "1",
volume = "45",
doi = "10.1111/ijlh.13969"
}

Tošić, N., Ugrin, M., Marjanović, I., Kostić, T., Vuković, V., Tomić, K., Otasević, V., Antić, D., Mihaljević, B., Pavlović, S.,& Karan-Đurašević, T.. (2023). Expression of BCL11A in chronic lymphocytic leukaemia. in International Journal of Laboratory Hematology
Wiley, Hoboken., 45(1), 64-71.
https://doi.org/10.1111/ijlh.13969

Tošić N, Ugrin M, Marjanović I, Kostić T, Vuković V, Tomić K, Otasević V, Antić D, Mihaljević B, Pavlović S, Karan-Đurašević T. Expression of BCL11A in chronic lymphocytic leukaemia. in International Journal of Laboratory Hematology. 2023;45(1):64-71.
doi:10.1111/ijlh.13969 .

Tošić, Nataša, Ugrin, Milena, Marjanović, Irena, Kostić, Tatjana, Vuković, Vojin, Tomić, Kristina, Otasević, Vladimir, Antić, Darko, Mihaljević, Biljana, Pavlović, Sonja, Karan-Đurašević, Teodora, "Expression of BCL11A in chronic lymphocytic leukaemia" in International Journal of Laboratory Hematology, 45, no. 1 (2023):64-71,
https://doi.org/10.1111/ijlh.13969 . .

TY  - JOUR
AU  - Jaković, Ljubomir
AU  - Fekete, Marija Dencic
AU  - Virijević, Marijana
AU  - Kraguljac Kurtović, Nada
AU  - Todorić-Zivanović, Biljana
AU  - Stamatović, Dragana
AU  - Karan-Đurašević, Teodora
AU  - Pavlović, Sonja
AU  - Leković, Danijela
AU  - Bogdanović, Andrija
PY  - 2022
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/1592
AB  - De novo AMLs with typical nonrandom chromosomal abnormalities are often associated with specific morphology subtypes. The t(8;21) is one of the most prominent recurrent cytogenetic aberrations (RCA) in AML, frequently associated with AML with maturation, and is characterized as a good prognostic marker. On the contrary, BCR::ABL1 rearrangement is rarely observed in AMLs, without specific morphology, carrying poor prognosis. Its distinction from blastic transformation of chronic myeloid leukemia has been a matter of long debate. The revised WHO classification (2016) recognized AML with BCR::ABL1(+) as a provisional entity. The occurrence of additional cytogenetic aberrations in AML RCA within the same leukemic clone has been detected, albeit rare cases of BCR::ABL1(+) were reported, mainly as subclones. Those additional cytogenetic and molecular findings seem to significantly affect patient prognosis. Conventional cytogenetic analysis, fluorescent in situ hybridization (FISH), and polymerase chain reaction (PCR) were applied at presentation and during the follow-up of the patient. We present a 34-year-old male patient with de novo AML harboring concomitant t(8;21) and t(9;22) in a single clone. The presence of both t(8;21) and Philadelphia chromosome (Ph+) in the same metaphases but in less than 100% of the analyzed cells, the p190 BCR::ABL transcript type, and absence of splenomegaly support that additional BCR::ABL1(+) is a part of the main leukemic clone. These findings, accompanied with an encouraging outcome of continuous cytogenetic and molecular remission after induction therapy, support BCR::ABL1 being a secondary genetic event in AML with t(8;21).
PB  - Heidelberg : Springer
T2  - Journal of Hematopathology
T1  - De novo acute myeloid leukemia harboring concomitant t(8;21)(q22;q22);RUNX1::RUNX1T1 and BCR::ABL1 (p190 minor transcript)
EP  - 195
IS  - 3
SP  - 191
VL  - 15
DO  - 10.1007/s12308-022-00509-4
ER  - 

@article{
author = "Jaković, Ljubomir and Fekete, Marija Dencic and Virijević, Marijana and Kraguljac Kurtović, Nada and Todorić-Zivanović, Biljana and Stamatović, Dragana and Karan-Đurašević, Teodora and Pavlović, Sonja and Leković, Danijela and Bogdanović, Andrija",
year = "2022",
abstract = "De novo AMLs with typical nonrandom chromosomal abnormalities are often associated with specific morphology subtypes. The t(8;21) is one of the most prominent recurrent cytogenetic aberrations (RCA) in AML, frequently associated with AML with maturation, and is characterized as a good prognostic marker. On the contrary, BCR::ABL1 rearrangement is rarely observed in AMLs, without specific morphology, carrying poor prognosis. Its distinction from blastic transformation of chronic myeloid leukemia has been a matter of long debate. The revised WHO classification (2016) recognized AML with BCR::ABL1(+) as a provisional entity. The occurrence of additional cytogenetic aberrations in AML RCA within the same leukemic clone has been detected, albeit rare cases of BCR::ABL1(+) were reported, mainly as subclones. Those additional cytogenetic and molecular findings seem to significantly affect patient prognosis. Conventional cytogenetic analysis, fluorescent in situ hybridization (FISH), and polymerase chain reaction (PCR) were applied at presentation and during the follow-up of the patient. We present a 34-year-old male patient with de novo AML harboring concomitant t(8;21) and t(9;22) in a single clone. The presence of both t(8;21) and Philadelphia chromosome (Ph+) in the same metaphases but in less than 100% of the analyzed cells, the p190 BCR::ABL transcript type, and absence of splenomegaly support that additional BCR::ABL1(+) is a part of the main leukemic clone. These findings, accompanied with an encouraging outcome of continuous cytogenetic and molecular remission after induction therapy, support BCR::ABL1 being a secondary genetic event in AML with t(8;21).",
publisher = "Heidelberg : Springer",
journal = "Journal of Hematopathology",
title = "De novo acute myeloid leukemia harboring concomitant t(8;21)(q22;q22);RUNX1::RUNX1T1 and BCR::ABL1 (p190 minor transcript)",
pages = "195-191",
number = "3",
volume = "15",
doi = "10.1007/s12308-022-00509-4"
}

Jaković, L., Fekete, M. D., Virijević, M., Kraguljac Kurtović, N., Todorić-Zivanović, B., Stamatović, D., Karan-Đurašević, T., Pavlović, S., Leković, D.,& Bogdanović, A.. (2022). De novo acute myeloid leukemia harboring concomitant t(8;21)(q22;q22);RUNX1::RUNX1T1 and BCR::ABL1 (p190 minor transcript). in Journal of Hematopathology
Heidelberg : Springer., 15(3), 191-195.
https://doi.org/10.1007/s12308-022-00509-4

Jaković L, Fekete MD, Virijević M, Kraguljac Kurtović N, Todorić-Zivanović B, Stamatović D, Karan-Đurašević T, Pavlović S, Leković D, Bogdanović A. De novo acute myeloid leukemia harboring concomitant t(8;21)(q22;q22);RUNX1::RUNX1T1 and BCR::ABL1 (p190 minor transcript). in Journal of Hematopathology. 2022;15(3):191-195.
doi:10.1007/s12308-022-00509-4 .

Jaković, Ljubomir, Fekete, Marija Dencic, Virijević, Marijana, Kraguljac Kurtović, Nada, Todorić-Zivanović, Biljana, Stamatović, Dragana, Karan-Đurašević, Teodora, Pavlović, Sonja, Leković, Danijela, Bogdanović, Andrija, "De novo acute myeloid leukemia harboring concomitant t(8;21)(q22;q22);RUNX1::RUNX1T1 and BCR::ABL1 (p190 minor transcript)" in Journal of Hematopathology, 15, no. 3 (2022):191-195,
https://doi.org/10.1007/s12308-022-00509-4 . .

TY  - JOUR
AU  - Gašić, Vladimir
AU  - Karan-Đurašević, Teodora
AU  - Pavlović, Đorđe
AU  - Zukić, Branka
AU  - Pavlović, Sonja
AU  - Tošić, Nataša
PY  - 2022
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/1660
AB  - Leukemia is a heterogenous group of hematological malignancies categorized in four main types (acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL), chronic myeloid leukemia (CML) and chronic lymphocytic leukemia (CLL). Several cytogenetic and molecular markers have become a part of routine analysis for leukemia patients. These markers have been used in diagnosis, risk-stratification and targeted therapy application. Recent studies have indicated that numerous regulatory RNAs, such as long non-coding RNAs (lncRNAs), have a role in tumor initiation and progression. When it comes to leukemia, data for lncRNA involvement in its etiology, progression, diagnosis, treatment and prognosis is limited. The aim of this review is to summarize research data on lncRNAs in different types of leukemia, on their expression pattern, their role in leukemic transformation and disease progression. The usefulness of this information in the clinical setting, i.e., for diagnostic and prognostic purposes, will be emphasized. Finally, how particular lncRNAs could be used as potential targets for the application of targeted therapy will be considered.
T2  - Life
T2  - Life
T1  - Diagnostic and Therapeutic Implications of Long Non-Coding RNAs in Leukemia
IS  - 11
SP  - 1770
VL  - 12
DO  - 10.3390/life12111770
ER  - 

@article{
author = "Gašić, Vladimir and Karan-Đurašević, Teodora and Pavlović, Đorđe and Zukić, Branka and Pavlović, Sonja and Tošić, Nataša",
year = "2022",
abstract = "Leukemia is a heterogenous group of hematological malignancies categorized in four main types (acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL), chronic myeloid leukemia (CML) and chronic lymphocytic leukemia (CLL). Several cytogenetic and molecular markers have become a part of routine analysis for leukemia patients. These markers have been used in diagnosis, risk-stratification and targeted therapy application. Recent studies have indicated that numerous regulatory RNAs, such as long non-coding RNAs (lncRNAs), have a role in tumor initiation and progression. When it comes to leukemia, data for lncRNA involvement in its etiology, progression, diagnosis, treatment and prognosis is limited. The aim of this review is to summarize research data on lncRNAs in different types of leukemia, on their expression pattern, their role in leukemic transformation and disease progression. The usefulness of this information in the clinical setting, i.e., for diagnostic and prognostic purposes, will be emphasized. Finally, how particular lncRNAs could be used as potential targets for the application of targeted therapy will be considered.",
journal = "Life, Life",
title = "Diagnostic and Therapeutic Implications of Long Non-Coding RNAs in Leukemia",
number = "11",
pages = "1770",
volume = "12",
doi = "10.3390/life12111770"
}

Gašić, V., Karan-Đurašević, T., Pavlović, Đ., Zukić, B., Pavlović, S.,& Tošić, N.. (2022). Diagnostic and Therapeutic Implications of Long Non-Coding RNAs in Leukemia. in Life, 12(11), 1770.
https://doi.org/10.3390/life12111770

Gašić V, Karan-Đurašević T, Pavlović Đ, Zukić B, Pavlović S, Tošić N. Diagnostic and Therapeutic Implications of Long Non-Coding RNAs in Leukemia. in Life. 2022;12(11):1770.
doi:10.3390/life12111770 .

Gašić, Vladimir, Karan-Đurašević, Teodora, Pavlović, Đorđe, Zukić, Branka, Pavlović, Sonja, Tošić, Nataša, "Diagnostic and Therapeutic Implications of Long Non-Coding RNAs in Leukemia" in Life, 12, no. 11 (2022):1770,
https://doi.org/10.3390/life12111770 . .

TY  - JOUR
AU  - Mihaljević, Biljana
AU  - Vuković, Vojin
AU  - Milić, Nataša
AU  - Karan-Đurašević, Teodora
AU  - Tošić, Nataša
AU  - Kostić, Tatjana
AU  - Marjanović, Irena
AU  - Denčić-Fekete, Marija
AU  - Đurašinović, Vladislava
AU  - Dragović-Ivančević, Tijana
AU  - Pavlović, Sonja
AU  - Antić, Darko
PY  - 2021
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/1458
AB  - Uvod/Cilj Prognoza hronične limfocitne leukemije (HLL) značajno je unapređena u poslednje vreme. Među nekoliko prognostičkih modela čiji je cilj predviđanje vremena do prve terapije (eng. TTFT) izdvajaju se skor rizika od progresije (eng. PRS) i skor Centra za rak MD Anderson iz 2011. God. (eng. MDACC 2011), dok se internacionalni prognostički indeks za HLL (eng. CLL-IPI), iako primarno ustanovljen za predikciju ukupnog preživljavanja (eng. OS), dobro pokazao i u predikciji TTFT. Cilj ovog rada je da se ispita značaj pomenutih prognostičkih modela u pogledu predviđanja TTFT i OS. Metode Analizirana kohorta je obuhvatila 57 neselektovanih bolesnika sa HLL Univerzitetskog kliničkog centra Srbije sa prosečno agresivnijim profilom bolesti u odnosu na opštu populaciju de novo bolesnika sa HLL. Bolesnici su ocenjivani prema navedenim skorovima uz analizu TTFT i OS. Rezultati Bolesnici sa višim vrednostima CLL-IPI, PRS i MDACC 2011 primili su prvu terapiju značajno ranije u poređenju sa bolesnicima sa nižim vrednostima ovih skorova (p = 0,002, p = 0,019 i p  lt  0,001, redom). U multivarijantnoj analizi, MDACC 2011 i CLL-IPI su zadržali prognostički značaj u predikciji TTFT (p = 0,001, odnosno p = 0,018), dok je PRS ovaj značaj izgubio. CLL-IPI je bio jedini značajan prediktor OS u univarijantnoj (p = 0,005) i u multivarijantnoj analizi (p = 0,013). Zaključak CLL-IPI, PRS i naročito MDACC 2011 su dobri prediktori TTFT čak i u kohortama bolesnika sa agresivnijom bolešću, dok je za predikciju OS od ova tri prognostička modela CLL-IPI jedini primenljiv. Ovi rezultati pokazuju da bi prognostičke modele trebalo ispitati na bolesnicima sa HLL u različitim fazama bolesti, kakvi se sreću u realnoj kliničkoj praksi.
AB  - Introduction/Objective Prognostication of chronic lymphocytic leukemia (CLL) has been substantially improved in recent times. Among several prognostic models (PMs) focused on the prediction of time to first treatment (TTFT), progression-risk score (PRS), and MD Anderson Cancer Center score 2011 (MDACC 2011) are the most relevant, while CLL-International Prognostic Index (CLL-IPI), although originally developed to predict overall survival (OS), is also being used to estimate TTFT. The aim of this study was to investigate CLL-IPI, PRS, and MDACC 2011 prognostic values regarding TTFT and OS. Methods The analyzed cohort included 57 unselected Serbian CLL patients from a single institution, with the basic characteristics reflecting more aggressive disease than in the general de novo CLL population. The eligible patients were assigned investigated PMs, and TTFT and OS analyses were performed. Results Patients with higher risk scores according to CLL-IPI, PRS, and MDACC 2011 underwent treatment significantly earlier than patients with lower risk scores (p = 0.002, p = 0.019, and p  lt  0.001, respectively). In multivariate analysis, MDACC 2011 and CLL-IPI retained their significance regarding TTFT (p = 0.001 and p = 0.018, respectively), while PRS did not. CLL-IPI was the only significant predictor of OS both at the univariate (p = 0.005) and multivariate (p = 0.013) levels. Conclusion CLL-IPI, PRS, and particularly MDACC 2011 are able to predict TTFT even in cohorts with more advanced-disease patients, while for prediction of OS, CLL-IPI is the only applicable among the three PMs. These results imply that PMs should be investigated in more diverse CLL populations, as it is in real-life setting.
PB  - Srpsko lekarsko društvo, Beograd
T2  - Srpski arhiv za celokupno lekarstvo
T1  - Uporedna analiza internacionalnog prognostičkog indeksa za hroničnu limfocitnu leukemiju, skora rizika od progresije i skora Centra za rak MD Anderson - iskustvo jednog centra
T1  - Comparative analysis of International Prognostic Index for chronic lymphocytic leukemia, progression-risk score, and MD Anderson Cancer Center 2011 score: A single center experience
EP  - 421
IS  - 7-8
SP  - 415
VL  - 149
DO  - 10.2298/SARH201005047M
ER  - 

@article{
author = "Mihaljević, Biljana and Vuković, Vojin and Milić, Nataša and Karan-Đurašević, Teodora and Tošić, Nataša and Kostić, Tatjana and Marjanović, Irena and Denčić-Fekete, Marija and Đurašinović, Vladislava and Dragović-Ivančević, Tijana and Pavlović, Sonja and Antić, Darko",
year = "2021",
abstract = "Uvod/Cilj Prognoza hronične limfocitne leukemije (HLL) značajno je unapređena u poslednje vreme. Među nekoliko prognostičkih modela čiji je cilj predviđanje vremena do prve terapije (eng. TTFT) izdvajaju se skor rizika od progresije (eng. PRS) i skor Centra za rak MD Anderson iz 2011. God. (eng. MDACC 2011), dok se internacionalni prognostički indeks za HLL (eng. CLL-IPI), iako primarno ustanovljen za predikciju ukupnog preživljavanja (eng. OS), dobro pokazao i u predikciji TTFT. Cilj ovog rada je da se ispita značaj pomenutih prognostičkih modela u pogledu predviđanja TTFT i OS. Metode Analizirana kohorta je obuhvatila 57 neselektovanih bolesnika sa HLL Univerzitetskog kliničkog centra Srbije sa prosečno agresivnijim profilom bolesti u odnosu na opštu populaciju de novo bolesnika sa HLL. Bolesnici su ocenjivani prema navedenim skorovima uz analizu TTFT i OS. Rezultati Bolesnici sa višim vrednostima CLL-IPI, PRS i MDACC 2011 primili su prvu terapiju značajno ranije u poređenju sa bolesnicima sa nižim vrednostima ovih skorova (p = 0,002, p = 0,019 i p  lt  0,001, redom). U multivarijantnoj analizi, MDACC 2011 i CLL-IPI su zadržali prognostički značaj u predikciji TTFT (p = 0,001, odnosno p = 0,018), dok je PRS ovaj značaj izgubio. CLL-IPI je bio jedini značajan prediktor OS u univarijantnoj (p = 0,005) i u multivarijantnoj analizi (p = 0,013). Zaključak CLL-IPI, PRS i naročito MDACC 2011 su dobri prediktori TTFT čak i u kohortama bolesnika sa agresivnijom bolešću, dok je za predikciju OS od ova tri prognostička modela CLL-IPI jedini primenljiv. Ovi rezultati pokazuju da bi prognostičke modele trebalo ispitati na bolesnicima sa HLL u različitim fazama bolesti, kakvi se sreću u realnoj kliničkoj praksi., Introduction/Objective Prognostication of chronic lymphocytic leukemia (CLL) has been substantially improved in recent times. Among several prognostic models (PMs) focused on the prediction of time to first treatment (TTFT), progression-risk score (PRS), and MD Anderson Cancer Center score 2011 (MDACC 2011) are the most relevant, while CLL-International Prognostic Index (CLL-IPI), although originally developed to predict overall survival (OS), is also being used to estimate TTFT. The aim of this study was to investigate CLL-IPI, PRS, and MDACC 2011 prognostic values regarding TTFT and OS. Methods The analyzed cohort included 57 unselected Serbian CLL patients from a single institution, with the basic characteristics reflecting more aggressive disease than in the general de novo CLL population. The eligible patients were assigned investigated PMs, and TTFT and OS analyses were performed. Results Patients with higher risk scores according to CLL-IPI, PRS, and MDACC 2011 underwent treatment significantly earlier than patients with lower risk scores (p = 0.002, p = 0.019, and p  lt  0.001, respectively). In multivariate analysis, MDACC 2011 and CLL-IPI retained their significance regarding TTFT (p = 0.001 and p = 0.018, respectively), while PRS did not. CLL-IPI was the only significant predictor of OS both at the univariate (p = 0.005) and multivariate (p = 0.013) levels. Conclusion CLL-IPI, PRS, and particularly MDACC 2011 are able to predict TTFT even in cohorts with more advanced-disease patients, while for prediction of OS, CLL-IPI is the only applicable among the three PMs. These results imply that PMs should be investigated in more diverse CLL populations, as it is in real-life setting.",
publisher = "Srpsko lekarsko društvo, Beograd",
journal = "Srpski arhiv za celokupno lekarstvo",
title = "Uporedna analiza internacionalnog prognostičkog indeksa za hroničnu limfocitnu leukemiju, skora rizika od progresije i skora Centra za rak MD Anderson - iskustvo jednog centra, Comparative analysis of International Prognostic Index for chronic lymphocytic leukemia, progression-risk score, and MD Anderson Cancer Center 2011 score: A single center experience",
pages = "421-415",
number = "7-8",
volume = "149",
doi = "10.2298/SARH201005047M"
}

Mihaljević, B., Vuković, V., Milić, N., Karan-Đurašević, T., Tošić, N., Kostić, T., Marjanović, I., Denčić-Fekete, M., Đurašinović, V., Dragović-Ivančević, T., Pavlović, S.,& Antić, D.. (2021). Uporedna analiza internacionalnog prognostičkog indeksa za hroničnu limfocitnu leukemiju, skora rizika od progresije i skora Centra za rak MD Anderson - iskustvo jednog centra. in Srpski arhiv za celokupno lekarstvo
Srpsko lekarsko društvo, Beograd., 149(7-8), 415-421.
https://doi.org/10.2298/SARH201005047M

Mihaljević B, Vuković V, Milić N, Karan-Đurašević T, Tošić N, Kostić T, Marjanović I, Denčić-Fekete M, Đurašinović V, Dragović-Ivančević T, Pavlović S, Antić D. Uporedna analiza internacionalnog prognostičkog indeksa za hroničnu limfocitnu leukemiju, skora rizika od progresije i skora Centra za rak MD Anderson - iskustvo jednog centra. in Srpski arhiv za celokupno lekarstvo. 2021;149(7-8):415-421.
doi:10.2298/SARH201005047M .

Mihaljević, Biljana, Vuković, Vojin, Milić, Nataša, Karan-Đurašević, Teodora, Tošić, Nataša, Kostić, Tatjana, Marjanović, Irena, Denčić-Fekete, Marija, Đurašinović, Vladislava, Dragović-Ivančević, Tijana, Pavlović, Sonja, Antić, Darko, "Uporedna analiza internacionalnog prognostičkog indeksa za hroničnu limfocitnu leukemiju, skora rizika od progresije i skora Centra za rak MD Anderson - iskustvo jednog centra" in Srpski arhiv za celokupno lekarstvo, 149, no. 7-8 (2021):415-421,
https://doi.org/10.2298/SARH201005047M . .

TY  - JOUR
AU  - Agathangelidis, Andreas
AU  - Chatzidimitriou, Anastasia
AU  - Gemenetzi, Katerina
AU  - Giudicelli, Veronique
AU  - Karypidou, Maria
AU  - Plevova, Karla
AU  - Davis, Zadie
AU  - Yan, Xiao-Jie
AU  - Jeromin, Sabine
AU  - Schneider, Christof
AU  - Pedersen, Lone Bredo
AU  - Tschumper, Renee C.
AU  - Sutton, Lesley-Ann
AU  - Baliakas, Panagiotis
AU  - Scarfo, Lydia
AU  - van Gastel, Ellen J.
AU  - Armand, Marine
AU  - Tausch, Eugen
AU  - Biderman, Bella
AU  - Baer, Constance
AU  - Bagnara, Davide
AU  - Navarro, Alba
AU  - de Septenville, Anne Langlois
AU  - Guido, Valentina
AU  - Mitterbauer-Hohendanner, Gerlinde
AU  - Dimovski, Aleksandar
AU  - Brieghel, Christian
AU  - Lawless, Sarah
AU  - Meggendorfer, Manja
AU  - Brazdilova, Kamila
AU  - Ritgen, Matthias
AU  - Facco, Monica
AU  - Tresoldi, Cristina
AU  - Visentin, Andrea
AU  - Patriarca, Andrea
AU  - Catherwood, Mark
AU  - Bonello, Lisa
AU  - Sudarikov, Andrey
AU  - Vanura, Katrina
AU  - Roumelioti, Maria
AU  - Francova, Hana Skuhrova
AU  - Moysiadis, Theodoros
AU  - Veronese, Silvio
AU  - Giannopoulos, Krzysztof
AU  - Mansouri, Larry
AU  - Karan-Đurašević, Teodora
AU  - Sandaltzopoulos, Raphael
AU  - Bodor, Csaba
AU  - Fais, Franco
AU  - Kater, Arnon
AU  - Panovska, Irina
AU  - Rossi, Davide
AU  - Alshemmari, Salem
AU  - Panagiotidis, Panagiotis
AU  - Costeas, Paul
AU  - Espinet, Blanca
AU  - Antić, Darko
AU  - Foroni, Letizia
AU  - Montillo, Marco
AU  - Trentin, Livio
AU  - Stavroyianni, Niki
AU  - Gaidano, Gianluca
AU  - di Celle, Paola Francia
AU  - Niemann, Carsten
AU  - Campo, Elias
AU  - Anagnostopoulos, Achilles
AU  - Pott, Christiane
AU  - Fischer, Kirsten
AU  - Hallek, Michael
AU  - Oscier, David
AU  - Stilgenbauer, Stephan
AU  - Haferlach, Claudia
AU  - Jelinek, Diane
AU  - Chiorazzi, Nicholas
AU  - Pospisilova, Sarka
AU  - Lefranc, Marie-Paule
AU  - Kossida, Sofia
AU  - Langerak, Anton W.
AU  - Belessi, Chrysoula
AU  - Davi, Frederic
AU  - Rosenquist, Richard
AU  - Ghia, Paolo
AU  - Stamatopoulos, Kostas
PY  - 2021
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/1427
AB  - Chronic lymphocytic leukemia (CLL) is characterized by the existence of subsets of patients with (quasi)identical, stereotyped B-cell receptor (BcR) immunoglobulins. Patients in certain major stereotyped subsets often display remarkably consistent clinicobiological profiles, suggesting that the study of BcR immunoglobulin stereotypy in CLL has important implications for understanding disease pathophysiology and refining clinical decision-making. Nevertheless, several issues remain open, especially pertaining to the actual frequency of BcR immunoglobulin stereotypy and major subsets, as well as the existence of higher-order connections between individual subsets. To address these issues, we investigated clonotypic IGHV-IGHD-IGHJ gene rearrangements in a series of 29 856 patients with CLL, by far the largest series worldwide. We report that the stereotyped fraction of CLL peaks at 41% of the entire cohort and that all 19 previously identified major subsets retained their relative size and ranking, while 10 new ones emerged; overall, major stereotyped subsets had a cumulative frequency of 13.5%. Higher-level relationships were evident between subsets, particularly for major stereotyped subsets with unmutated IGHV genes (U-CLL), for which close relations with other subsets, termed "satellites," were identified. Satellite subsets accounted for 3% of the entire cohort. These results confirm our previous notion that major subsets can be robustly identified and are consistent in relative size, hence representing distinct disease variants amenable to compartmentalized research with the potential of overcoming the pronounced heterogeneity of CLL. Furthermore, the existence of satellite subsets reveals a novel aspect of repertoire restriction with implications for refined molecular classification of CLL.
PB  - Amer Soc Hematology, Washington
T2  - Blood
T1  - Higher-order connections between stereotyped subsets: implications for improved patient classification in CLL
EP  - 1376
IS  - 10
SP  - 1365
VL  - 137
DO  - 10.1182/blood.2020007039
ER  - 

@article{
author = "Agathangelidis, Andreas and Chatzidimitriou, Anastasia and Gemenetzi, Katerina and Giudicelli, Veronique and Karypidou, Maria and Plevova, Karla and Davis, Zadie and Yan, Xiao-Jie and Jeromin, Sabine and Schneider, Christof and Pedersen, Lone Bredo and Tschumper, Renee C. and Sutton, Lesley-Ann and Baliakas, Panagiotis and Scarfo, Lydia and van Gastel, Ellen J. and Armand, Marine and Tausch, Eugen and Biderman, Bella and Baer, Constance and Bagnara, Davide and Navarro, Alba and de Septenville, Anne Langlois and Guido, Valentina and Mitterbauer-Hohendanner, Gerlinde and Dimovski, Aleksandar and Brieghel, Christian and Lawless, Sarah and Meggendorfer, Manja and Brazdilova, Kamila and Ritgen, Matthias and Facco, Monica and Tresoldi, Cristina and Visentin, Andrea and Patriarca, Andrea and Catherwood, Mark and Bonello, Lisa and Sudarikov, Andrey and Vanura, Katrina and Roumelioti, Maria and Francova, Hana Skuhrova and Moysiadis, Theodoros and Veronese, Silvio and Giannopoulos, Krzysztof and Mansouri, Larry and Karan-Đurašević, Teodora and Sandaltzopoulos, Raphael and Bodor, Csaba and Fais, Franco and Kater, Arnon and Panovska, Irina and Rossi, Davide and Alshemmari, Salem and Panagiotidis, Panagiotis and Costeas, Paul and Espinet, Blanca and Antić, Darko and Foroni, Letizia and Montillo, Marco and Trentin, Livio and Stavroyianni, Niki and Gaidano, Gianluca and di Celle, Paola Francia and Niemann, Carsten and Campo, Elias and Anagnostopoulos, Achilles and Pott, Christiane and Fischer, Kirsten and Hallek, Michael and Oscier, David and Stilgenbauer, Stephan and Haferlach, Claudia and Jelinek, Diane and Chiorazzi, Nicholas and Pospisilova, Sarka and Lefranc, Marie-Paule and Kossida, Sofia and Langerak, Anton W. and Belessi, Chrysoula and Davi, Frederic and Rosenquist, Richard and Ghia, Paolo and Stamatopoulos, Kostas",
year = "2021",
abstract = "Chronic lymphocytic leukemia (CLL) is characterized by the existence of subsets of patients with (quasi)identical, stereotyped B-cell receptor (BcR) immunoglobulins. Patients in certain major stereotyped subsets often display remarkably consistent clinicobiological profiles, suggesting that the study of BcR immunoglobulin stereotypy in CLL has important implications for understanding disease pathophysiology and refining clinical decision-making. Nevertheless, several issues remain open, especially pertaining to the actual frequency of BcR immunoglobulin stereotypy and major subsets, as well as the existence of higher-order connections between individual subsets. To address these issues, we investigated clonotypic IGHV-IGHD-IGHJ gene rearrangements in a series of 29 856 patients with CLL, by far the largest series worldwide. We report that the stereotyped fraction of CLL peaks at 41% of the entire cohort and that all 19 previously identified major subsets retained their relative size and ranking, while 10 new ones emerged; overall, major stereotyped subsets had a cumulative frequency of 13.5%. Higher-level relationships were evident between subsets, particularly for major stereotyped subsets with unmutated IGHV genes (U-CLL), for which close relations with other subsets, termed "satellites," were identified. Satellite subsets accounted for 3% of the entire cohort. These results confirm our previous notion that major subsets can be robustly identified and are consistent in relative size, hence representing distinct disease variants amenable to compartmentalized research with the potential of overcoming the pronounced heterogeneity of CLL. Furthermore, the existence of satellite subsets reveals a novel aspect of repertoire restriction with implications for refined molecular classification of CLL.",
publisher = "Amer Soc Hematology, Washington",
journal = "Blood",
title = "Higher-order connections between stereotyped subsets: implications for improved patient classification in CLL",
pages = "1376-1365",
number = "10",
volume = "137",
doi = "10.1182/blood.2020007039"
}

Agathangelidis, A., Chatzidimitriou, A., Gemenetzi, K., Giudicelli, V., Karypidou, M., Plevova, K., Davis, Z., Yan, X., Jeromin, S., Schneider, C., Pedersen, L. B., Tschumper, R. C., Sutton, L., Baliakas, P., Scarfo, L., van Gastel, E. J., Armand, M., Tausch, E., Biderman, B., Baer, C., Bagnara, D., Navarro, A., de Septenville, A. L., Guido, V., Mitterbauer-Hohendanner, G., Dimovski, A., Brieghel, C., Lawless, S., Meggendorfer, M., Brazdilova, K., Ritgen, M., Facco, M., Tresoldi, C., Visentin, A., Patriarca, A., Catherwood, M., Bonello, L., Sudarikov, A., Vanura, K., Roumelioti, M., Francova, H. S., Moysiadis, T., Veronese, S., Giannopoulos, K., Mansouri, L., Karan-Đurašević, T., Sandaltzopoulos, R., Bodor, C., Fais, F., Kater, A., Panovska, I., Rossi, D., Alshemmari, S., Panagiotidis, P., Costeas, P., Espinet, B., Antić, D., Foroni, L., Montillo, M., Trentin, L., Stavroyianni, N., Gaidano, G., di Celle, P. F., Niemann, C., Campo, E., Anagnostopoulos, A., Pott, C., Fischer, K., Hallek, M., Oscier, D., Stilgenbauer, S., Haferlach, C., Jelinek, D., Chiorazzi, N., Pospisilova, S., Lefranc, M., Kossida, S., Langerak, A. W., Belessi, C., Davi, F., Rosenquist, R., Ghia, P.,& Stamatopoulos, K.. (2021). Higher-order connections between stereotyped subsets: implications for improved patient classification in CLL. in Blood
Amer Soc Hematology, Washington., 137(10), 1365-1376.
https://doi.org/10.1182/blood.2020007039

Agathangelidis A, Chatzidimitriou A, Gemenetzi K, Giudicelli V, Karypidou M, Plevova K, Davis Z, Yan X, Jeromin S, Schneider C, Pedersen LB, Tschumper RC, Sutton L, Baliakas P, Scarfo L, van Gastel EJ, Armand M, Tausch E, Biderman B, Baer C, Bagnara D, Navarro A, de Septenville AL, Guido V, Mitterbauer-Hohendanner G, Dimovski A, Brieghel C, Lawless S, Meggendorfer M, Brazdilova K, Ritgen M, Facco M, Tresoldi C, Visentin A, Patriarca A, Catherwood M, Bonello L, Sudarikov A, Vanura K, Roumelioti M, Francova HS, Moysiadis T, Veronese S, Giannopoulos K, Mansouri L, Karan-Đurašević T, Sandaltzopoulos R, Bodor C, Fais F, Kater A, Panovska I, Rossi D, Alshemmari S, Panagiotidis P, Costeas P, Espinet B, Antić D, Foroni L, Montillo M, Trentin L, Stavroyianni N, Gaidano G, di Celle PF, Niemann C, Campo E, Anagnostopoulos A, Pott C, Fischer K, Hallek M, Oscier D, Stilgenbauer S, Haferlach C, Jelinek D, Chiorazzi N, Pospisilova S, Lefranc M, Kossida S, Langerak AW, Belessi C, Davi F, Rosenquist R, Ghia P, Stamatopoulos K. Higher-order connections between stereotyped subsets: implications for improved patient classification in CLL. in Blood. 2021;137(10):1365-1376.
doi:10.1182/blood.2020007039 .

Agathangelidis, Andreas, Chatzidimitriou, Anastasia, Gemenetzi, Katerina, Giudicelli, Veronique, Karypidou, Maria, Plevova, Karla, Davis, Zadie, Yan, Xiao-Jie, Jeromin, Sabine, Schneider, Christof, Pedersen, Lone Bredo, Tschumper, Renee C., Sutton, Lesley-Ann, Baliakas, Panagiotis, Scarfo, Lydia, van Gastel, Ellen J., Armand, Marine, Tausch, Eugen, Biderman, Bella, Baer, Constance, Bagnara, Davide, Navarro, Alba, de Septenville, Anne Langlois, Guido, Valentina, Mitterbauer-Hohendanner, Gerlinde, Dimovski, Aleksandar, Brieghel, Christian, Lawless, Sarah, Meggendorfer, Manja, Brazdilova, Kamila, Ritgen, Matthias, Facco, Monica, Tresoldi, Cristina, Visentin, Andrea, Patriarca, Andrea, Catherwood, Mark, Bonello, Lisa, Sudarikov, Andrey, Vanura, Katrina, Roumelioti, Maria, Francova, Hana Skuhrova, Moysiadis, Theodoros, Veronese, Silvio, Giannopoulos, Krzysztof, Mansouri, Larry, Karan-Đurašević, Teodora, Sandaltzopoulos, Raphael, Bodor, Csaba, Fais, Franco, Kater, Arnon, Panovska, Irina, Rossi, Davide, Alshemmari, Salem, Panagiotidis, Panagiotis, Costeas, Paul, Espinet, Blanca, Antić, Darko, Foroni, Letizia, Montillo, Marco, Trentin, Livio, Stavroyianni, Niki, Gaidano, Gianluca, di Celle, Paola Francia, Niemann, Carsten, Campo, Elias, Anagnostopoulos, Achilles, Pott, Christiane, Fischer, Kirsten, Hallek, Michael, Oscier, David, Stilgenbauer, Stephan, Haferlach, Claudia, Jelinek, Diane, Chiorazzi, Nicholas, Pospisilova, Sarka, Lefranc, Marie-Paule, Kossida, Sofia, Langerak, Anton W., Belessi, Chrysoula, Davi, Frederic, Rosenquist, Richard, Ghia, Paolo, Stamatopoulos, Kostas, "Higher-order connections between stereotyped subsets: implications for improved patient classification in CLL" in Blood, 137, no. 10 (2021):1365-1376,
https://doi.org/10.1182/blood.2020007039 . .

TY  - JOUR
AU  - Marjanović, Irena
AU  - Karan-Đurašević, Teodora
AU  - Kostić, Tatjana
AU  - Virijević, Marijana
AU  - Suvajdžić-Vuković, Nada
AU  - Pavlović, Sonja
AU  - Tošić, Nataša
PY  - 2021
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/1506
AB  - Introduction Acute myeloid leukemia with normal karyotype (AML-NK) is the largest group of AML patients with very heterogeneous disease outcome. In order to ensure more precise risk stratification new molecular markers have been introduced, like expression level for BAALC (Brain and Acute Leukemia, Cytoplasmic) and MN1 (Meningioma 1) genes. Methods In this study, we investigated expression level of both genes in 111 adult AML-NK at diagnosis and examined their prognostic potential. Results BAALC and MN1 expression were detected in about one third of the patients, and positive correlation between these two genes was found. The BAALC(+)/or MN1(+) status was not associated with the presence of FLT3-ITD mutations, but exhibited strong correlation with NPM1(wt) status (P  lt  .001). Therefore, among BAALC(+)/or MN1(+) patients the most frequent ones were FLT3-ITD-/NPM1(-) double negative patients with intermediate prognosis. When BAALC(+)/or MN1(+) patients were divided into BAALC(high)/BAALC(low) (21/21) and MN1(high)/MN1(low) (21/22) groups, we detected that BAALC(high)/or MN1(high) patients had a tendency toward lower complete remission rate. Also, survival analysis showed that BAALC(high)/or MN1(high) patients had shorter disease-free survival and overall survival (OS). The most pronounced influence on prognosis was detected in FLT3-ITD-/NPM1(-) group of patients that are lacking reliable prognostic markers, where OS in BAALC(high)/or MN1(high) was only 5 months vs 25 months in BAALC(low)/or MN1(low). Conclusion These findings indicate that BAALC and MN1 expression level could be used for more precise risk stratification of AML-NK patients and especially FLT3-ITD-/NPM1(-) patients, transforming this intermediate-risk group, into a group with an adverse prognosis.
PB  - Wiley, Hoboken
T2  - International Journal of Laboratory Hematology
T1  - Prognostic significance of combined BAALC and MN1 gene expression level in acute myeloid leukemia with normal karyotype
EP  - 440
IS  - 3
SP  - 433
VL  - 43
DO  - 10.1111/ijlh.13405
ER  - 

@article{
author = "Marjanović, Irena and Karan-Đurašević, Teodora and Kostić, Tatjana and Virijević, Marijana and Suvajdžić-Vuković, Nada and Pavlović, Sonja and Tošić, Nataša",
year = "2021",
abstract = "Introduction Acute myeloid leukemia with normal karyotype (AML-NK) is the largest group of AML patients with very heterogeneous disease outcome. In order to ensure more precise risk stratification new molecular markers have been introduced, like expression level for BAALC (Brain and Acute Leukemia, Cytoplasmic) and MN1 (Meningioma 1) genes. Methods In this study, we investigated expression level of both genes in 111 adult AML-NK at diagnosis and examined their prognostic potential. Results BAALC and MN1 expression were detected in about one third of the patients, and positive correlation between these two genes was found. The BAALC(+)/or MN1(+) status was not associated with the presence of FLT3-ITD mutations, but exhibited strong correlation with NPM1(wt) status (P  lt  .001). Therefore, among BAALC(+)/or MN1(+) patients the most frequent ones were FLT3-ITD-/NPM1(-) double negative patients with intermediate prognosis. When BAALC(+)/or MN1(+) patients were divided into BAALC(high)/BAALC(low) (21/21) and MN1(high)/MN1(low) (21/22) groups, we detected that BAALC(high)/or MN1(high) patients had a tendency toward lower complete remission rate. Also, survival analysis showed that BAALC(high)/or MN1(high) patients had shorter disease-free survival and overall survival (OS). The most pronounced influence on prognosis was detected in FLT3-ITD-/NPM1(-) group of patients that are lacking reliable prognostic markers, where OS in BAALC(high)/or MN1(high) was only 5 months vs 25 months in BAALC(low)/or MN1(low). Conclusion These findings indicate that BAALC and MN1 expression level could be used for more precise risk stratification of AML-NK patients and especially FLT3-ITD-/NPM1(-) patients, transforming this intermediate-risk group, into a group with an adverse prognosis.",
publisher = "Wiley, Hoboken",
journal = "International Journal of Laboratory Hematology",
title = "Prognostic significance of combined BAALC and MN1 gene expression level in acute myeloid leukemia with normal karyotype",
pages = "440-433",
number = "3",
volume = "43",
doi = "10.1111/ijlh.13405"
}

Marjanović, I., Karan-Đurašević, T., Kostić, T., Virijević, M., Suvajdžić-Vuković, N., Pavlović, S.,& Tošić, N.. (2021). Prognostic significance of combined BAALC and MN1 gene expression level in acute myeloid leukemia with normal karyotype. in International Journal of Laboratory Hematology
Wiley, Hoboken., 43(3), 433-440.
https://doi.org/10.1111/ijlh.13405

Marjanović I, Karan-Đurašević T, Kostić T, Virijević M, Suvajdžić-Vuković N, Pavlović S, Tošić N. Prognostic significance of combined BAALC and MN1 gene expression level in acute myeloid leukemia with normal karyotype. in International Journal of Laboratory Hematology. 2021;43(3):433-440.
doi:10.1111/ijlh.13405 .

Marjanović, Irena, Karan-Đurašević, Teodora, Kostić, Tatjana, Virijević, Marijana, Suvajdžić-Vuković, Nada, Pavlović, Sonja, Tošić, Nataša, "Prognostic significance of combined BAALC and MN1 gene expression level in acute myeloid leukemia with normal karyotype" in International Journal of Laboratory Hematology, 43, no. 3 (2021):433-440,
https://doi.org/10.1111/ijlh.13405 . .

TY  - JOUR
AU  - Janić, Dragana
AU  - Perić, Jelena
AU  - Karan-Đurašević, Teodora
AU  - Kostić, Tatjana
AU  - Marjanović, Irena
AU  - Stanić, Bojana
AU  - Pejanović, Nadja
AU  - Dokmanović, Lidija
AU  - Lazić, Jelena
AU  - Krstovski, Nada
AU  - Virijević, Marijana
AU  - Tomin, Dragica
AU  - Vidović, Ana
AU  - Suvajdžić-Vuković, Nada
AU  - Pavlović, Sonja
AU  - Tošić, Nataša
PY  - 2020
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/1303
AB  - lt b gt Uvod: lt /b gt  Akutna limfoblastna leukemija (ALL) je najčešće maligno oboljenje kod dece, dok je kod odraslih njena učestalost mnogo niža. U današnjoj kliničkoj praksi kao najvažnije metode stratifikacije pacijenata u određene grupe rizika koriste se metode identifikacije citogenetičkih aberacija i malog broja molekulanih markera. Tehnologija sekvenciranja nove generacije (SNG) obezbeđuje veliku količinu podataka koji doprinose razjašnjavanju mutacionog profila dečje (dALL) i adultne ALL (aALL).  lt b gt Metode: lt /b gt  Uzorci DNK iz 34 dALL i aALL pacijenata analizirani su primenom SNG ciljanog sekvenciranja ("TruSeq Amplicon Cancer Panel - TSACP") kojim se sekvenciraju "hotspot" mutacije u 48 gena povezanih sa kancerom.  lt b gt Rezultati: lt /b gt  Identifikovano je ukupno 330 varijanti u kodirajućim regionima, od kojih je samo 95 njih za posledicu imalo potencijalnu promenu u proteinu. Posmatrano kod pojedinačnih pacijenata, detektovane mutacije su pretežno remetile Ras/RTK signalni put (STK11, KIT, MET, NRAS, KRAS, PTEN). Pored toga, identifikovano je 5 pacijenata sa istom mutacijom u HNF1A genu, koja je uzrokovala poremećaje u Wnt i Notch signalnom putu. Kod dva pa cijenta otkrivene su varijante u NOTCH1 genu. Nije detektovano istovremeno prisustvo varijanti u HNF1A i NOTCH1 genu, dok su geni uključeni u Ras/RTK signalni put pokazali tendenciju ka akumuliranju mutacija.  lt b gt Zaključak: lt /b gt  Naši rezultati pokazuju da ALL sadrži Mali broj mutacija, bez značajnih razlika između dALL i aALL (medijana po pacijentu 2 odnosno 3). Detektovane mutacije izazivaju poremećaje u nekoliko ključnih signalnih puteva, prvenstveno Ras/RTK kaskade. Ova studija doprinosi ukupnom znanju o mutacionom profilu ALL, što vodi ka boljem razumijevanju molekularne osnove ovog oboljenja.
AB  - lt b gt Background: lt /b gt  Acute lymphoblastic leukemia (ALL) is the most common cancer in children, whereas it is less common in adults. Identification of cytogenetic aberrations and a small number of molecular abnormalities are still the most important risk and therapy stratification methods in clinical practice today. Next generation sequencing (NGS) technology provides a large amount of data contributing to elucidation of mutational landscape of childhood (cALL) and adult ALL (aALL).  lt b gt Methods: lt /b gt  We analyzed DNA samples from 34 cALL and aALL patients, using NGS targeted sequencing TruSeq Amplicon - Cancer Panel (TSACP) which targets mutational hotspots in 48 cancer related genes.  lt b gt Results: lt /b gt  We identified a total of 330 variants in the coding regions, out of which only 95 were potentially protein-changing. Observed in individual patients, detected mutations predominantly disrupted Ras/RTK pathway (STK11, KIT, MET, NRAS, KRAS, PTEN). Additionally, we identified 5 patients with the same mutation in HNF1A gene, disrupting both Wnt and Notch signaling pathway. In two patients we detected variants in NOTCH1 gene. HNF1A and NOTCH1 variants were mutually exclusive, while genes involved in Ras/RTK pathway exhibit a tendency of mutation accumulation.  lt b gt Conclusions: lt /b gt  Our results showed that ALL contains low number of mutations, without significant differences between cALL and aALL (median per patient 2 and 3, respectively). Detected mutations affect few key signaling pathways, primarily Ras/RTK cascade. This study contributes to knowledge of ALL mutational landscape, leading to better understanding of molecular basis of this disease.
PB  - Društvo medicinskih biohemičara Srbije, Beograd i Versita
T2  - Journal of Medical Biochemistry
T1  - Primena ciljanog sekvenciranja nove generacije u analizi mutacionog profila pacijenata sa akutnom limfoblastnom leukemijom
T1  - Application of targeted next generation sequencing for the mutational profiling of patients with acute lymphoblastic leukemia
EP  - 82
IS  - 1
SP  - 72
VL  - 39
DO  - 10.2478/jomb-2019-0017
ER  - 

@article{
author = "Janić, Dragana and Perić, Jelena and Karan-Đurašević, Teodora and Kostić, Tatjana and Marjanović, Irena and Stanić, Bojana and Pejanović, Nadja and Dokmanović, Lidija and Lazić, Jelena and Krstovski, Nada and Virijević, Marijana and Tomin, Dragica and Vidović, Ana and Suvajdžić-Vuković, Nada and Pavlović, Sonja and Tošić, Nataša",
year = "2020",
abstract = "lt b gt Uvod: lt /b gt  Akutna limfoblastna leukemija (ALL) je najčešće maligno oboljenje kod dece, dok je kod odraslih njena učestalost mnogo niža. U današnjoj kliničkoj praksi kao najvažnije metode stratifikacije pacijenata u određene grupe rizika koriste se metode identifikacije citogenetičkih aberacija i malog broja molekulanih markera. Tehnologija sekvenciranja nove generacije (SNG) obezbeđuje veliku količinu podataka koji doprinose razjašnjavanju mutacionog profila dečje (dALL) i adultne ALL (aALL).  lt b gt Metode: lt /b gt  Uzorci DNK iz 34 dALL i aALL pacijenata analizirani su primenom SNG ciljanog sekvenciranja ("TruSeq Amplicon Cancer Panel - TSACP") kojim se sekvenciraju "hotspot" mutacije u 48 gena povezanih sa kancerom.  lt b gt Rezultati: lt /b gt  Identifikovano je ukupno 330 varijanti u kodirajućim regionima, od kojih je samo 95 njih za posledicu imalo potencijalnu promenu u proteinu. Posmatrano kod pojedinačnih pacijenata, detektovane mutacije su pretežno remetile Ras/RTK signalni put (STK11, KIT, MET, NRAS, KRAS, PTEN). Pored toga, identifikovano je 5 pacijenata sa istom mutacijom u HNF1A genu, koja je uzrokovala poremećaje u Wnt i Notch signalnom putu. Kod dva pa cijenta otkrivene su varijante u NOTCH1 genu. Nije detektovano istovremeno prisustvo varijanti u HNF1A i NOTCH1 genu, dok su geni uključeni u Ras/RTK signalni put pokazali tendenciju ka akumuliranju mutacija.  lt b gt Zaključak: lt /b gt  Naši rezultati pokazuju da ALL sadrži Mali broj mutacija, bez značajnih razlika između dALL i aALL (medijana po pacijentu 2 odnosno 3). Detektovane mutacije izazivaju poremećaje u nekoliko ključnih signalnih puteva, prvenstveno Ras/RTK kaskade. Ova studija doprinosi ukupnom znanju o mutacionom profilu ALL, što vodi ka boljem razumijevanju molekularne osnove ovog oboljenja., lt b gt Background: lt /b gt  Acute lymphoblastic leukemia (ALL) is the most common cancer in children, whereas it is less common in adults. Identification of cytogenetic aberrations and a small number of molecular abnormalities are still the most important risk and therapy stratification methods in clinical practice today. Next generation sequencing (NGS) technology provides a large amount of data contributing to elucidation of mutational landscape of childhood (cALL) and adult ALL (aALL).  lt b gt Methods: lt /b gt  We analyzed DNA samples from 34 cALL and aALL patients, using NGS targeted sequencing TruSeq Amplicon - Cancer Panel (TSACP) which targets mutational hotspots in 48 cancer related genes.  lt b gt Results: lt /b gt  We identified a total of 330 variants in the coding regions, out of which only 95 were potentially protein-changing. Observed in individual patients, detected mutations predominantly disrupted Ras/RTK pathway (STK11, KIT, MET, NRAS, KRAS, PTEN). Additionally, we identified 5 patients with the same mutation in HNF1A gene, disrupting both Wnt and Notch signaling pathway. In two patients we detected variants in NOTCH1 gene. HNF1A and NOTCH1 variants were mutually exclusive, while genes involved in Ras/RTK pathway exhibit a tendency of mutation accumulation.  lt b gt Conclusions: lt /b gt  Our results showed that ALL contains low number of mutations, without significant differences between cALL and aALL (median per patient 2 and 3, respectively). Detected mutations affect few key signaling pathways, primarily Ras/RTK cascade. This study contributes to knowledge of ALL mutational landscape, leading to better understanding of molecular basis of this disease.",
publisher = "Društvo medicinskih biohemičara Srbije, Beograd i Versita",
journal = "Journal of Medical Biochemistry",
title = "Primena ciljanog sekvenciranja nove generacije u analizi mutacionog profila pacijenata sa akutnom limfoblastnom leukemijom, Application of targeted next generation sequencing for the mutational profiling of patients with acute lymphoblastic leukemia",
pages = "82-72",
number = "1",
volume = "39",
doi = "10.2478/jomb-2019-0017"
}

Janić, D., Perić, J., Karan-Đurašević, T., Kostić, T., Marjanović, I., Stanić, B., Pejanović, N., Dokmanović, L., Lazić, J., Krstovski, N., Virijević, M., Tomin, D., Vidović, A., Suvajdžić-Vuković, N., Pavlović, S.,& Tošić, N.. (2020). Primena ciljanog sekvenciranja nove generacije u analizi mutacionog profila pacijenata sa akutnom limfoblastnom leukemijom. in Journal of Medical Biochemistry
Društvo medicinskih biohemičara Srbije, Beograd i Versita., 39(1), 72-82.
https://doi.org/10.2478/jomb-2019-0017

Janić D, Perić J, Karan-Đurašević T, Kostić T, Marjanović I, Stanić B, Pejanović N, Dokmanović L, Lazić J, Krstovski N, Virijević M, Tomin D, Vidović A, Suvajdžić-Vuković N, Pavlović S, Tošić N. Primena ciljanog sekvenciranja nove generacije u analizi mutacionog profila pacijenata sa akutnom limfoblastnom leukemijom. in Journal of Medical Biochemistry. 2020;39(1):72-82.
doi:10.2478/jomb-2019-0017 .

Janić, Dragana, Perić, Jelena, Karan-Đurašević, Teodora, Kostić, Tatjana, Marjanović, Irena, Stanić, Bojana, Pejanović, Nadja, Dokmanović, Lidija, Lazić, Jelena, Krstovski, Nada, Virijević, Marijana, Tomin, Dragica, Vidović, Ana, Suvajdžić-Vuković, Nada, Pavlović, Sonja, Tošić, Nataša, "Primena ciljanog sekvenciranja nove generacije u analizi mutacionog profila pacijenata sa akutnom limfoblastnom leukemijom" in Journal of Medical Biochemistry, 39, no. 1 (2020):72-82,
https://doi.org/10.2478/jomb-2019-0017 . .

TY  - JOUR
AU  - Vesovic, Natasa
AU  - Tošić, Nataša
AU  - Karan-Đurašević, Teodora
AU  - Andric, Zoran
AU  - Zdravkovic, Darko
AU  - Pavlović, Sonja
AU  - Jovanovic, Dragana
PY  - 2020
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/1642
AB  - Introduction:  The finding that long noncoding RNAs (lncRNAs) originating from tumor cells could be found in general circulation has prompted the idea to use lncRNAs as noninvasive diagnostic biomarkers of particular diseases. In this study we explored the expression pattern of circulating GAS5...
T2  - Archives of Medical Science
T2  - Archives of Medical ScienceArch Med Sci
T1  - Expression pattern of circulating long non-coding RNA GAS5 as a novel biomarker in non-small cell lung cancer patients
EP  - 7
SP  - 1
DO  - 10.5114/aoms.2020.98815
ER  - 

@article{
author = "Vesovic, Natasa and Tošić, Nataša and Karan-Đurašević, Teodora and Andric, Zoran and Zdravkovic, Darko and Pavlović, Sonja and Jovanovic, Dragana",
year = "2020",
abstract = "Introduction:  The finding that long noncoding RNAs (lncRNAs) originating from tumor cells could be found in general circulation has prompted the idea to use lncRNAs as noninvasive diagnostic biomarkers of particular diseases. In this study we explored the expression pattern of circulating GAS5...",
journal = "Archives of Medical Science, Archives of Medical ScienceArch Med Sci",
title = "Expression pattern of circulating long non-coding RNA GAS5 as a novel biomarker in non-small cell lung cancer patients",
pages = "7-1",
doi = "10.5114/aoms.2020.98815"
}

Vesovic, N., Tošić, N., Karan-Đurašević, T., Andric, Z., Zdravkovic, D., Pavlović, S.,& Jovanovic, D.. (2020). Expression pattern of circulating long non-coding RNA GAS5 as a novel biomarker in non-small cell lung cancer patients. in Archives of Medical Science, 1-7.
https://doi.org/10.5114/aoms.2020.98815

Vesovic N, Tošić N, Karan-Đurašević T, Andric Z, Zdravkovic D, Pavlović S, Jovanovic D. Expression pattern of circulating long non-coding RNA GAS5 as a novel biomarker in non-small cell lung cancer patients. in Archives of Medical Science. 2020;:1-7.
doi:10.5114/aoms.2020.98815 .

Vesovic, Natasa, Tošić, Nataša, Karan-Đurašević, Teodora, Andric, Zoran, Zdravkovic, Darko, Pavlović, Sonja, Jovanovic, Dragana, "Expression pattern of circulating long non-coding RNA GAS5 as a novel biomarker in non-small cell lung cancer patients" in Archives of Medical Science (2020):1-7,
https://doi.org/10.5114/aoms.2020.98815 . .

TY  - JOUR
AU  - Vuković, Vojin
AU  - Karan-Đurašević, Teodora
AU  - Antić, Darko
AU  - Tošić, Nataša
AU  - Kostić, Tatjana
AU  - Marjanović, Irena
AU  - Denčić-Fekete, Marija
AU  - Đurašinović, Vladislava
AU  - Pavlović, Sonja
AU  - Mihaljević, Biljana
PY  - 2020
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/1321
AB  - Fludarabine plus cyclophosphamide (FC) chemotherapy is the basis of treatment protocols used in management of chronic lymphocytic leukemia (CLL). In some patients, response to therapy may be affected by aberrant function of genes involved in pharmacokinetics and pharmacodynamics of the drugs. The aim of this research was to assess the impact of pharmacogenetic variability, namely expression of SLC28A3 gene and the presence of CYP2B6*6 variant allele, on the FC treatment efficacy. Forty-four CLL patients with functional TP53 gene at the time of FC initiation were enrolled in this study. CYP2B6 genotyping was performed by polymerase chain reaction and direct sequencing. SLC28A3 expression was measured by quantitative reverse-transcriptase polymerase chain reaction. Significantly higher pretreatment levels of SLC28A3 mRNA were detected in patients who failed to respond to FC in comparison to patients who achieved complete and partial response (p = 0.01). SLC28A3 high-expressing cases were almost ten times more likely not to respond to FC than low-expressing cases (OR = 9.8; p = 0.046). However, association of SLC28A3 expression with progression-free survival (PFS) and overall survival (OS) was not observed. CYP2B6*6 allele, detected in 24 patients (54.6%), exerted no association with the attainment of response to FC, as well as with PFS and OS. The results of this study demonstrate that SLC28A3 expression is a significant predictor of FC efficacy in CLL patients with intact TP53. Elevated SLC28A3 mRNA levels are associated with inferior short-term response to FC, suggesting that, if validated on larger cohorts, SLC28A3 expression may become a biomarker useful for pretreatment stratification of patients.
PB  - Frontiers Media Sa, Lausanne
T2  - Pathology & Oncology Research
T1  - Association of SLC28A3 Gene Expression and CYP2B6*6 Allele with the Response to Fludarabine Plus Cyclophosphamide in Chronic Lymphocytic Leukemia Patients
EP  - 752
IS  - 2
SP  - 743
VL  - 26
DO  - 10.1007/s12253-019-00613-4
ER  - 

@article{
author = "Vuković, Vojin and Karan-Đurašević, Teodora and Antić, Darko and Tošić, Nataša and Kostić, Tatjana and Marjanović, Irena and Denčić-Fekete, Marija and Đurašinović, Vladislava and Pavlović, Sonja and Mihaljević, Biljana",
year = "2020",
abstract = "Fludarabine plus cyclophosphamide (FC) chemotherapy is the basis of treatment protocols used in management of chronic lymphocytic leukemia (CLL). In some patients, response to therapy may be affected by aberrant function of genes involved in pharmacokinetics and pharmacodynamics of the drugs. The aim of this research was to assess the impact of pharmacogenetic variability, namely expression of SLC28A3 gene and the presence of CYP2B6*6 variant allele, on the FC treatment efficacy. Forty-four CLL patients with functional TP53 gene at the time of FC initiation were enrolled in this study. CYP2B6 genotyping was performed by polymerase chain reaction and direct sequencing. SLC28A3 expression was measured by quantitative reverse-transcriptase polymerase chain reaction. Significantly higher pretreatment levels of SLC28A3 mRNA were detected in patients who failed to respond to FC in comparison to patients who achieved complete and partial response (p = 0.01). SLC28A3 high-expressing cases were almost ten times more likely not to respond to FC than low-expressing cases (OR = 9.8; p = 0.046). However, association of SLC28A3 expression with progression-free survival (PFS) and overall survival (OS) was not observed. CYP2B6*6 allele, detected in 24 patients (54.6%), exerted no association with the attainment of response to FC, as well as with PFS and OS. The results of this study demonstrate that SLC28A3 expression is a significant predictor of FC efficacy in CLL patients with intact TP53. Elevated SLC28A3 mRNA levels are associated with inferior short-term response to FC, suggesting that, if validated on larger cohorts, SLC28A3 expression may become a biomarker useful for pretreatment stratification of patients.",
publisher = "Frontiers Media Sa, Lausanne",
journal = "Pathology & Oncology Research",
title = "Association of SLC28A3 Gene Expression and CYP2B6*6 Allele with the Response to Fludarabine Plus Cyclophosphamide in Chronic Lymphocytic Leukemia Patients",
pages = "752-743",
number = "2",
volume = "26",
doi = "10.1007/s12253-019-00613-4"
}

Vuković, V., Karan-Đurašević, T., Antić, D., Tošić, N., Kostić, T., Marjanović, I., Denčić-Fekete, M., Đurašinović, V., Pavlović, S.,& Mihaljević, B.. (2020). Association of SLC28A3 Gene Expression and CYP2B6*6 Allele with the Response to Fludarabine Plus Cyclophosphamide in Chronic Lymphocytic Leukemia Patients. in Pathology & Oncology Research
Frontiers Media Sa, Lausanne., 26(2), 743-752.
https://doi.org/10.1007/s12253-019-00613-4

Vuković V, Karan-Đurašević T, Antić D, Tošić N, Kostić T, Marjanović I, Denčić-Fekete M, Đurašinović V, Pavlović S, Mihaljević B. Association of SLC28A3 Gene Expression and CYP2B6*6 Allele with the Response to Fludarabine Plus Cyclophosphamide in Chronic Lymphocytic Leukemia Patients. in Pathology & Oncology Research. 2020;26(2):743-752.
doi:10.1007/s12253-019-00613-4 .

Vuković, Vojin, Karan-Đurašević, Teodora, Antić, Darko, Tošić, Nataša, Kostić, Tatjana, Marjanović, Irena, Denčić-Fekete, Marija, Đurašinović, Vladislava, Pavlović, Sonja, Mihaljević, Biljana, "Association of SLC28A3 Gene Expression and CYP2B6*6 Allele with the Response to Fludarabine Plus Cyclophosphamide in Chronic Lymphocytic Leukemia Patients" in Pathology & Oncology Research, 26, no. 2 (2020):743-752,
https://doi.org/10.1007/s12253-019-00613-4 . .

TY  - JOUR
AU  - Tomić, Kristina
AU  - Karan-Đurašević, Teodora
AU  - Vuković, Vojin
AU  - Mihaljević, Biljana
AU  - Antić, Darko
PY  - 2020
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/1346
AB  - Hronična limfocitna leukemija (HLL) izuzetno je heterogena bolest varijabilnog kliničkog toka. S jedne strane imamo, pacijente sa agresivnom i rezistentnom bolešću od koje umiru svega par meseci nakon dijagnoze, dok s druge strane spektra postoje pacijenti sa indolentnom, sporo progredirajućom bolešću koja ne zahteva lečenje decenijama. Razlozi su samo delimično poznati i već su decenijama unazad tema mnogobrojnih naučnih istraživanja. Tako je razvijen koncept prognostičkih i prediktivnih faktora u HLL-u, koji imaju za cilj da predvide klinički tok, odnosno terapijski ishod HLL-a. Liste prognostičkih i prediktivnih faktora su, sa boljim poznavanjem patofiziologije ove bolesti, svakom godinom sve duže, ali se i međusobno preklapaju. U ovom revijalnom radu izabrali smo aberacije TP53 gena i mutacioni status rearanžiranih IGHV (engl. immunoglobulin heavy variable) gena kao dva najznačajnija i najproučavanija faktora koji imaju i prognostički i prediktivni značaj.
AB  - Chronic lymphocytic leukemia (CLL) is a very heterogeneous disease with a variable clinical course. On the one side of the spectrum, there are patients with aggressive and resistant disease, of which they die only a few months after diagnosis while, on the other side, there are patients with an indolent, slowly progressive disease that does not require treatment for decades. The reasons for this are only partially known, but they have been the subject of numerous scientific studies during the last several decades. Consequently, the concept of prognostic and predictive factors in CLL have emerged, which aims to predict the clinical course and its therapeutic outcome. With the improvement of understanding the pathophysiology of this disease, the lists of prognostic and predictive factors are getting longer every year, but they also overlap. In this review, we singled out the aberrations of the TP53 gene and the IGHV (immunoglobulin heavy variable) gene mutational status as the two most important and most studied factors that have both prognostic and predictive significance.
PB  - Univerzitet u Beogradu - Medicinski fakultet, Beograd
T2  - Medicinski podmladak
T1  - Klinički značaj aberacija TP53 gena i IGHV mutacionog statusa u hroničnoj limfocitnoj leukemiji
T1  - Clinical significance of TP53 aberrations and IGHV mutational status in chronic lymphocytic leukemia
EP  - 53
IS  - 4
SP  - 47
VL  - 71
DO  - 10.5937/mp71-28969
ER  - 

@article{
author = "Tomić, Kristina and Karan-Đurašević, Teodora and Vuković, Vojin and Mihaljević, Biljana and Antić, Darko",
year = "2020",
abstract = "Hronična limfocitna leukemija (HLL) izuzetno je heterogena bolest varijabilnog kliničkog toka. S jedne strane imamo, pacijente sa agresivnom i rezistentnom bolešću od koje umiru svega par meseci nakon dijagnoze, dok s druge strane spektra postoje pacijenti sa indolentnom, sporo progredirajućom bolešću koja ne zahteva lečenje decenijama. Razlozi su samo delimično poznati i već su decenijama unazad tema mnogobrojnih naučnih istraživanja. Tako je razvijen koncept prognostičkih i prediktivnih faktora u HLL-u, koji imaju za cilj da predvide klinički tok, odnosno terapijski ishod HLL-a. Liste prognostičkih i prediktivnih faktora su, sa boljim poznavanjem patofiziologije ove bolesti, svakom godinom sve duže, ali se i međusobno preklapaju. U ovom revijalnom radu izabrali smo aberacije TP53 gena i mutacioni status rearanžiranih IGHV (engl. immunoglobulin heavy variable) gena kao dva najznačajnija i najproučavanija faktora koji imaju i prognostički i prediktivni značaj., Chronic lymphocytic leukemia (CLL) is a very heterogeneous disease with a variable clinical course. On the one side of the spectrum, there are patients with aggressive and resistant disease, of which they die only a few months after diagnosis while, on the other side, there are patients with an indolent, slowly progressive disease that does not require treatment for decades. The reasons for this are only partially known, but they have been the subject of numerous scientific studies during the last several decades. Consequently, the concept of prognostic and predictive factors in CLL have emerged, which aims to predict the clinical course and its therapeutic outcome. With the improvement of understanding the pathophysiology of this disease, the lists of prognostic and predictive factors are getting longer every year, but they also overlap. In this review, we singled out the aberrations of the TP53 gene and the IGHV (immunoglobulin heavy variable) gene mutational status as the two most important and most studied factors that have both prognostic and predictive significance.",
publisher = "Univerzitet u Beogradu - Medicinski fakultet, Beograd",
journal = "Medicinski podmladak",
title = "Klinički značaj aberacija TP53 gena i IGHV mutacionog statusa u hroničnoj limfocitnoj leukemiji, Clinical significance of TP53 aberrations and IGHV mutational status in chronic lymphocytic leukemia",
pages = "53-47",
number = "4",
volume = "71",
doi = "10.5937/mp71-28969"
}

Tomić, K., Karan-Đurašević, T., Vuković, V., Mihaljević, B.,& Antić, D.. (2020). Klinički značaj aberacija TP53 gena i IGHV mutacionog statusa u hroničnoj limfocitnoj leukemiji. in Medicinski podmladak
Univerzitet u Beogradu - Medicinski fakultet, Beograd., 71(4), 47-53.
https://doi.org/10.5937/mp71-28969

Tomić K, Karan-Đurašević T, Vuković V, Mihaljević B, Antić D. Klinički značaj aberacija TP53 gena i IGHV mutacionog statusa u hroničnoj limfocitnoj leukemiji. in Medicinski podmladak. 2020;71(4):47-53.
doi:10.5937/mp71-28969 .

Tomić, Kristina, Karan-Đurašević, Teodora, Vuković, Vojin, Mihaljević, Biljana, Antić, Darko, "Klinički značaj aberacija TP53 gena i IGHV mutacionog statusa u hroničnoj limfocitnoj leukemiji" in Medicinski podmladak, 71, no. 4 (2020):47-53,
https://doi.org/10.5937/mp71-28969 . .

TY  - JOUR
AU  - Marjanović, Irena
AU  - Karan-Đurašević, Teodora
AU  - Kostić, Tatjana
AU  - Virijević, Marijana
AU  - Suvajdžić-Vuković, Nada
AU  - Pavlović, Sonja
AU  - Tošić, Nataša
PY  - 2020
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/1391
AB  - According to current criteria, patients with acute myeloid leukemia with normal karyotype (AML-NK) are classified as intermediate risk patients. There is a constant need for additional molecular markers that will help in substratification into more precise prognostic groups. One of the potential new markers is Ecotropic viral integration 1 site (EVI1) transcriptional factor, whose expression is dissregulated in abnormal hematopoietic process. The purpose of this study was to examine EVI1 gene expression in 104 adult AML-NK patients and on 10 healthy bone marrow donors using real-time polymerase chain reaction method, and to evaluate association between EVI1 expression level and other molecular and clinical features, and to examine its potential influence on the prognosis of the disease. Overexpression of EVI1 gene (EVI1(+) status) was present in 17% of patients. Increased EVI1 expression was predominantly found in patients with lower WBC count (P = 0.003) and lower bone marrow blast percentage (P = 0.005). EVI1(+) patients had lower WT1 expression level (P = 0.041), and were negative for FLT3-ITD and NPM1 mutations (P = 0.036 and P = 0.003). Patients with EVI1(+) status had higher complete remission rate (P = 0.047), but EVI1 expression didn't influence overall and disease free survival. EVI1 expression status alone, cannot be used as a new marker for more precise substratification of AML-NK patients. Further investigations conducted on larger number of patients may indicate how EVI1 expression could influence the prognosis and outcome of AML-NK patients, by itself, or in the context of other molecular and clinical parameters.
PB  - Springer India, New Delhi
T2  - Indian Journal of Hematology and Blood Transfusion
T1  - Expression Pattern and Prognostic Significance of EVI1 Gene in Adult Acute Myeloid Leukemia Patients with Normal Karyotype
EP  - 299
IS  - 2
SP  - 292
VL  - 36
DO  - 10.1007/s12288-019-01227-1
ER  - 

@article{
author = "Marjanović, Irena and Karan-Đurašević, Teodora and Kostić, Tatjana and Virijević, Marijana and Suvajdžić-Vuković, Nada and Pavlović, Sonja and Tošić, Nataša",
year = "2020",
abstract = "According to current criteria, patients with acute myeloid leukemia with normal karyotype (AML-NK) are classified as intermediate risk patients. There is a constant need for additional molecular markers that will help in substratification into more precise prognostic groups. One of the potential new markers is Ecotropic viral integration 1 site (EVI1) transcriptional factor, whose expression is dissregulated in abnormal hematopoietic process. The purpose of this study was to examine EVI1 gene expression in 104 adult AML-NK patients and on 10 healthy bone marrow donors using real-time polymerase chain reaction method, and to evaluate association between EVI1 expression level and other molecular and clinical features, and to examine its potential influence on the prognosis of the disease. Overexpression of EVI1 gene (EVI1(+) status) was present in 17% of patients. Increased EVI1 expression was predominantly found in patients with lower WBC count (P = 0.003) and lower bone marrow blast percentage (P = 0.005). EVI1(+) patients had lower WT1 expression level (P = 0.041), and were negative for FLT3-ITD and NPM1 mutations (P = 0.036 and P = 0.003). Patients with EVI1(+) status had higher complete remission rate (P = 0.047), but EVI1 expression didn't influence overall and disease free survival. EVI1 expression status alone, cannot be used as a new marker for more precise substratification of AML-NK patients. Further investigations conducted on larger number of patients may indicate how EVI1 expression could influence the prognosis and outcome of AML-NK patients, by itself, or in the context of other molecular and clinical parameters.",
publisher = "Springer India, New Delhi",
journal = "Indian Journal of Hematology and Blood Transfusion",
title = "Expression Pattern and Prognostic Significance of EVI1 Gene in Adult Acute Myeloid Leukemia Patients with Normal Karyotype",
pages = "299-292",
number = "2",
volume = "36",
doi = "10.1007/s12288-019-01227-1"
}

Marjanović, I., Karan-Đurašević, T., Kostić, T., Virijević, M., Suvajdžić-Vuković, N., Pavlović, S.,& Tošić, N.. (2020). Expression Pattern and Prognostic Significance of EVI1 Gene in Adult Acute Myeloid Leukemia Patients with Normal Karyotype. in Indian Journal of Hematology and Blood Transfusion
Springer India, New Delhi., 36(2), 292-299.
https://doi.org/10.1007/s12288-019-01227-1

Marjanović I, Karan-Đurašević T, Kostić T, Virijević M, Suvajdžić-Vuković N, Pavlović S, Tošić N. Expression Pattern and Prognostic Significance of EVI1 Gene in Adult Acute Myeloid Leukemia Patients with Normal Karyotype. in Indian Journal of Hematology and Blood Transfusion. 2020;36(2):292-299.
doi:10.1007/s12288-019-01227-1 .

Marjanović, Irena, Karan-Đurašević, Teodora, Kostić, Tatjana, Virijević, Marijana, Suvajdžić-Vuković, Nada, Pavlović, Sonja, Tošić, Nataša, "Expression Pattern and Prognostic Significance of EVI1 Gene in Adult Acute Myeloid Leukemia Patients with Normal Karyotype" in Indian Journal of Hematology and Blood Transfusion, 36, no. 2 (2020):292-299,
https://doi.org/10.1007/s12288-019-01227-1 . .

TY  - JOUR
AU  - Nikčević, Gordana
AU  - Srzentić Dražilov, Sanja
AU  - Karan-Đurašević, Teodora
AU  - Tošić, Nataša
AU  - Kontos, Christos K.
AU  - Scorilas, Andreas
AU  - Pavlović, Sonja
PY  - 2020
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/1326
AB  - The BCL2L12, one of the latest discovered members of the BCL2 family, has both pro- and anti-apoptotic roles that are cell-type-dependent. Its role in tumorigenesis is highly implicated. Sixty-three splice variants of this gene have been identified so far, with significant differences in expression patterns between various cancer cell lines. Presently, little is known regarding the regulation of expression of the BCL2L12 gene. For the vast majority of BCL2L12 gene splice variants, the 5'- and 3'-untranslated regions as well as their transcriptional regulation have not been determined yet. The aim of this study was to get insight into the regulation of the BCL2L12 gene transcription in human chronic myelogenous leukemia (K562) cell line. Our results point to the activity of novel transcription start site of the BCL2L12 gene and indicate that Sp1 and GATA-1 transcription factors could be involved in the regulation of BCL2L12 gene expression in K562 cells. The previously reported active promoter of BCL2L12 gene differs from the one we described in our study. If this novel BCL2L12 promoter is confirmed to be active in other malignancies, transcripts generated from this region could be considered as new cancer-specific biomarkers. The results of our study contribute to the better understanding of the transcriptional regulation of the BCL2L12 gene.
PB  - Elsevier, Amsterdam
T2  - Gene
T1  - Complex transcriptional regulation of the BCL2L12 gene: Novel, active promoter in K562 cells
VL  - 750
DO  - 10.1016/j.gene.2020.144723
ER  - 

@article{
author = "Nikčević, Gordana and Srzentić Dražilov, Sanja and Karan-Đurašević, Teodora and Tošić, Nataša and Kontos, Christos K. and Scorilas, Andreas and Pavlović, Sonja",
year = "2020",
abstract = "The BCL2L12, one of the latest discovered members of the BCL2 family, has both pro- and anti-apoptotic roles that are cell-type-dependent. Its role in tumorigenesis is highly implicated. Sixty-three splice variants of this gene have been identified so far, with significant differences in expression patterns between various cancer cell lines. Presently, little is known regarding the regulation of expression of the BCL2L12 gene. For the vast majority of BCL2L12 gene splice variants, the 5'- and 3'-untranslated regions as well as their transcriptional regulation have not been determined yet. The aim of this study was to get insight into the regulation of the BCL2L12 gene transcription in human chronic myelogenous leukemia (K562) cell line. Our results point to the activity of novel transcription start site of the BCL2L12 gene and indicate that Sp1 and GATA-1 transcription factors could be involved in the regulation of BCL2L12 gene expression in K562 cells. The previously reported active promoter of BCL2L12 gene differs from the one we described in our study. If this novel BCL2L12 promoter is confirmed to be active in other malignancies, transcripts generated from this region could be considered as new cancer-specific biomarkers. The results of our study contribute to the better understanding of the transcriptional regulation of the BCL2L12 gene.",
publisher = "Elsevier, Amsterdam",
journal = "Gene",
title = "Complex transcriptional regulation of the BCL2L12 gene: Novel, active promoter in K562 cells",
volume = "750",
doi = "10.1016/j.gene.2020.144723"
}

Nikčević, G., Srzentić Dražilov, S., Karan-Đurašević, T., Tošić, N., Kontos, C. K., Scorilas, A.,& Pavlović, S.. (2020). Complex transcriptional regulation of the BCL2L12 gene: Novel, active promoter in K562 cells. in Gene
Elsevier, Amsterdam., 750.
https://doi.org/10.1016/j.gene.2020.144723

Nikčević G, Srzentić Dražilov S, Karan-Đurašević T, Tošić N, Kontos CK, Scorilas A, Pavlović S. Complex transcriptional regulation of the BCL2L12 gene: Novel, active promoter in K562 cells. in Gene. 2020;750.
doi:10.1016/j.gene.2020.144723 .

Nikčević, Gordana, Srzentić Dražilov, Sanja, Karan-Đurašević, Teodora, Tošić, Nataša, Kontos, Christos K., Scorilas, Andreas, Pavlović, Sonja, "Complex transcriptional regulation of the BCL2L12 gene: Novel, active promoter in K562 cells" in Gene, 750 (2020),
https://doi.org/10.1016/j.gene.2020.144723 . .