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  - JOUR
AU  - Jovanović, Aleksa
AU  - Tošić, Nataša
AU  - Marjanović, Irena
AU  - Komazec, Jovana
AU  - Zukić, Branka
AU  - Nikitović, Marina
AU  - Ilić, Rosanda
AU  - Grujičić, Danica
AU  - Janić, Dragana
AU  - Pavlović, Sonja
PY  - 2023
UR  - https://www.mdpi.com/1422-0067/24/24/17387
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/2279
AB  - Central nervous system (CNS) tumors comprise around 20% of childhood malignancies. Germline variants in cancer predisposition genes (CPGs) are found in approximately 10% of pediatric patients with CNS tumors. This study aimed to characterize variants in CPGs in pediatric patients with CNS tumors and correlate these findings with clinically relevant data. Genomic DNA was isolated from the peripheral blood of 51 pediatric patients and further analyzed by the next-generation sequencing approach. Bioinformatic analysis was done using an “in-house” gene list panel, which included 144 genes related to pediatric brain tumors, and the gene list panel Neoplasm (HP:0002664). Our study found that 27% of pediatric patients with CNS tumors have a germline variant in some of the known CPGs, like ALK, APC, CHEK2, ELP1, MLH1, MSH2, NF1, NF2 and TP53. This study represents the first comprehensive evaluation of germline variants in pediatric patients with CNS tumors in the Western Balkans region. Our results indicate the necessity of genomic research to reveal the genetic basis of pediatric CNS tumors, as well as to define targets for the application and development of innovative therapeutics that form the basis of the upcoming era of personalized medicine.
T2  - International Journal of Molecular Sciences
T1  - Germline Variants in Cancer Predisposition Genes in Pediatric Patients with Central Nervous System Tumors
IS  - 24
SP  - 17387
VL  - 24
DO  - 10.3390/ijms242417387
ER  - 

@article{
author = "Jovanović, Aleksa and Tošić, Nataša and Marjanović, Irena and Komazec, Jovana and Zukić, Branka and Nikitović, Marina and Ilić, Rosanda and Grujičić, Danica and Janić, Dragana and Pavlović, Sonja",
year = "2023",
abstract = "Central nervous system (CNS) tumors comprise around 20% of childhood malignancies. Germline variants in cancer predisposition genes (CPGs) are found in approximately 10% of pediatric patients with CNS tumors. This study aimed to characterize variants in CPGs in pediatric patients with CNS tumors and correlate these findings with clinically relevant data. Genomic DNA was isolated from the peripheral blood of 51 pediatric patients and further analyzed by the next-generation sequencing approach. Bioinformatic analysis was done using an “in-house” gene list panel, which included 144 genes related to pediatric brain tumors, and the gene list panel Neoplasm (HP:0002664). Our study found that 27% of pediatric patients with CNS tumors have a germline variant in some of the known CPGs, like ALK, APC, CHEK2, ELP1, MLH1, MSH2, NF1, NF2 and TP53. This study represents the first comprehensive evaluation of germline variants in pediatric patients with CNS tumors in the Western Balkans region. Our results indicate the necessity of genomic research to reveal the genetic basis of pediatric CNS tumors, as well as to define targets for the application and development of innovative therapeutics that form the basis of the upcoming era of personalized medicine.",
journal = "International Journal of Molecular Sciences",
title = "Germline Variants in Cancer Predisposition Genes in Pediatric Patients with Central Nervous System Tumors",
number = "24",
pages = "17387",
volume = "24",
doi = "10.3390/ijms242417387"
}

Jovanović, A., Tošić, N., Marjanović, I., Komazec, J., Zukić, B., Nikitović, M., Ilić, R., Grujičić, D., Janić, D.,& Pavlović, S.. (2023). Germline Variants in Cancer Predisposition Genes in Pediatric Patients with Central Nervous System Tumors. in International Journal of Molecular Sciences, 24(24), 17387.
https://doi.org/10.3390/ijms242417387

Jovanović A, Tošić N, Marjanović I, Komazec J, Zukić B, Nikitović M, Ilić R, Grujičić D, Janić D, Pavlović S. Germline Variants in Cancer Predisposition Genes in Pediatric Patients with Central Nervous System Tumors. in International Journal of Molecular Sciences. 2023;24(24):17387.
doi:10.3390/ijms242417387 .

Jovanović, Aleksa, Tošić, Nataša, Marjanović, Irena, Komazec, Jovana, Zukić, Branka, Nikitović, Marina, Ilić, Rosanda, Grujičić, Danica, Janić, Dragana, Pavlović, Sonja, "Germline Variants in Cancer Predisposition Genes in Pediatric Patients with Central Nervous System Tumors" in International Journal of Molecular Sciences, 24, no. 24 (2023):17387,
https://doi.org/10.3390/ijms242417387 . .

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  - 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  - 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  - 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  - CONF
AU  - Anđelković, Marina
AU  - Klaassen, Kristel
AU  - Skakić, Anita
AU  - Marjanović, Irena
AU  - Kravljana, Ruzica
AU  - Đorđević, Maja
PY  - 2023
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/2179
AB  - Background: Childhood epilepsies are
caused by heterogeneous underlying disorders where
approximately 40% can be attributed to genetic
factors. Application of next-generation sequencing
(NGS) has revolutionized diagnostics and therefore
has enabled the identification of disease-causing
genes and variants in childhood epilepsies.
Materials and Methods: Patients who presented
with epilepsy of unknown etiology in childhood,
with suspicion of a genetic cause were included
in this study. In total, 55 patients from unrelated
non-consanguineous families were included and analyzed
by NGS either using clinical-exome sequencing
(MiSeq, Illumina) or whole-exome sequencing
(DNBSEQ-G400, MGI). Variants were prioritized
using Variant Interpreter and VarSome and classified
according to the ACMG recommendations.
Results: Using CES we analyzed 38 patients,
and for 22 of them a diagnosis was established.
Using WES we analyzed 17 patients with childhood epilepsy, which led to the identification of
disease-causing genes in 11 patients. The diagnostic
success rate for CES was 55.3% (21/38) and the
diagnostic rate for WES was 64.7% (11/17), with
the overall diagnostic rate being 58.2% (32/55). For
these patients, we detected pathogenic, likely pathogenic
variants or VUS in 24 epilepsy genes that
correlate well to the observed phenotype. Sixteen
novel genetic variants were identified and characterized
using various in silico algorithms.
Conclusion: This is the first study reporting
the molecular-genetic basis of childhood epilepsy
in Serbia. The prompt establishment of a specific
diagnosis is essential in order to make available the
prognosis, optimize therapy, and enable counseling
on recurrence risk in future pregnancies.
PB  - Macedonian Academy of Sciences and Arts
C3  - International Journal of Medical Genetics
T1  - CHARACTERIZATION OF 16 NOVEL GENETIC VARIANTS IN GENES RELATED TO CHILDHOOD EPILEPSIES
EP  - 114
IS  - Supplement
SP  - 114
VL  - 26
UR  - https://hdl.handle.net/21.15107/rcub_imagine_2179
ER  - 

@conference{
author = "Anđelković, Marina and Klaassen, Kristel and Skakić, Anita and Marjanović, Irena and Kravljana, Ruzica and Đorđević, Maja",
year = "2023",
abstract = "Background: Childhood epilepsies are
caused by heterogeneous underlying disorders where
approximately 40% can be attributed to genetic
factors. Application of next-generation sequencing
(NGS) has revolutionized diagnostics and therefore
has enabled the identification of disease-causing
genes and variants in childhood epilepsies.
Materials and Methods: Patients who presented
with epilepsy of unknown etiology in childhood,
with suspicion of a genetic cause were included
in this study. In total, 55 patients from unrelated
non-consanguineous families were included and analyzed
by NGS either using clinical-exome sequencing
(MiSeq, Illumina) or whole-exome sequencing
(DNBSEQ-G400, MGI). Variants were prioritized
using Variant Interpreter and VarSome and classified
according to the ACMG recommendations.
Results: Using CES we analyzed 38 patients,
and for 22 of them a diagnosis was established.
Using WES we analyzed 17 patients with childhood epilepsy, which led to the identification of
disease-causing genes in 11 patients. The diagnostic
success rate for CES was 55.3% (21/38) and the
diagnostic rate for WES was 64.7% (11/17), with
the overall diagnostic rate being 58.2% (32/55). For
these patients, we detected pathogenic, likely pathogenic
variants or VUS in 24 epilepsy genes that
correlate well to the observed phenotype. Sixteen
novel genetic variants were identified and characterized
using various in silico algorithms.
Conclusion: This is the first study reporting
the molecular-genetic basis of childhood epilepsy
in Serbia. The prompt establishment of a specific
diagnosis is essential in order to make available the
prognosis, optimize therapy, and enable counseling
on recurrence risk in future pregnancies.",
publisher = "Macedonian Academy of Sciences and Arts",
journal = "International Journal of Medical Genetics",
title = "CHARACTERIZATION OF 16 NOVEL GENETIC VARIANTS IN GENES RELATED TO CHILDHOOD EPILEPSIES",
pages = "114-114",
number = "Supplement",
volume = "26",
url = "https://hdl.handle.net/21.15107/rcub_imagine_2179"
}

Anđelković, M., Klaassen, K., Skakić, A., Marjanović, I., Kravljana, R.,& Đorđević, M.. (2023). CHARACTERIZATION OF 16 NOVEL GENETIC VARIANTS IN GENES RELATED TO CHILDHOOD EPILEPSIES. in International Journal of Medical Genetics
Macedonian Academy of Sciences and Arts., 26(Supplement), 114-114.
https://hdl.handle.net/21.15107/rcub_imagine_2179

Anđelković M, Klaassen K, Skakić A, Marjanović I, Kravljana R, Đorđević M. CHARACTERIZATION OF 16 NOVEL GENETIC VARIANTS IN GENES RELATED TO CHILDHOOD EPILEPSIES. in International Journal of Medical Genetics. 2023;26(Supplement):114-114.
https://hdl.handle.net/21.15107/rcub_imagine_2179 .

Anđelković, Marina, Klaassen, Kristel, Skakić, Anita, Marjanović, Irena, Kravljana, Ruzica, Đorđević, Maja, "CHARACTERIZATION OF 16 NOVEL GENETIC VARIANTS IN GENES RELATED TO CHILDHOOD EPILEPSIES" in International Journal of Medical Genetics, 26, no. Supplement (2023):114-114,
https://hdl.handle.net/21.15107/rcub_imagine_2179 .

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  - JOUR
AU  - Tošic, Natasa
AU  - Marjanović, Irena
AU  - Lazić, Jelena
PY  - 2023
UR  - https://www.sciencedirect.com/science/article/pii/S0006295223002964
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/2103
AB  - Acute myeloid leukemia (AML) is a very heterogeneous hematological malignancy that accounts for approximately 20% of all pediatric leukemia cases. The outcome of pediatric AML has improved over the last decades, with overall survival rates reaching up to 70%. Still, AML is among the leading types of pediatric cancers by its high mortality rate. Modulation of standard therapy, like chemotherapy intensification, hematopoietic stem cell transplantation and optimized supportive care, could only get this far, but for the significant improvement of the outcome in pediatric AML, development of novel targeted therapy approaches is necessary. In recent years the advances in genomic techniques have greatly expanded our knowledge of the AML biology, revealing molecular landscape and complexity of the disease, which in turn have led to the identification of novel therapeutic targets. This review provides a brief overview of the genetic landscape of pediatric AML, and how it’s used for precise molecular characterization and risk stratification of the patients, and also for the development of effective targeted therapy. Furthermore, this review presents recent advances in molecular targeted therapy and immunotherapy with an emphasis on the therapeutic approaches with significant clinical benefits for pediatric AML.
T2  - Biochemical Pharmacology
T1  - Pediatric acute myeloid leukemia: Insight into genetic landscape and novel targeted approaches
SP  - 115705
VL  - 215
DO  - 10.1016/j.bcp.2023.115705
ER  - 

@article{
author = "Tošic, Natasa and Marjanović, Irena and Lazić, Jelena",
year = "2023",
abstract = "Acute myeloid leukemia (AML) is a very heterogeneous hematological malignancy that accounts for approximately 20% of all pediatric leukemia cases. The outcome of pediatric AML has improved over the last decades, with overall survival rates reaching up to 70%. Still, AML is among the leading types of pediatric cancers by its high mortality rate. Modulation of standard therapy, like chemotherapy intensification, hematopoietic stem cell transplantation and optimized supportive care, could only get this far, but for the significant improvement of the outcome in pediatric AML, development of novel targeted therapy approaches is necessary. In recent years the advances in genomic techniques have greatly expanded our knowledge of the AML biology, revealing molecular landscape and complexity of the disease, which in turn have led to the identification of novel therapeutic targets. This review provides a brief overview of the genetic landscape of pediatric AML, and how it’s used for precise molecular characterization and risk stratification of the patients, and also for the development of effective targeted therapy. Furthermore, this review presents recent advances in molecular targeted therapy and immunotherapy with an emphasis on the therapeutic approaches with significant clinical benefits for pediatric AML.",
journal = "Biochemical Pharmacology",
title = "Pediatric acute myeloid leukemia: Insight into genetic landscape and novel targeted approaches",
pages = "115705",
volume = "215",
doi = "10.1016/j.bcp.2023.115705"
}

Tošic, N., Marjanović, I.,& Lazić, J.. (2023). Pediatric acute myeloid leukemia: Insight into genetic landscape and novel targeted approaches. in Biochemical Pharmacology, 215, 115705.
https://doi.org/10.1016/j.bcp.2023.115705

Tošic N, Marjanović I, Lazić J. Pediatric acute myeloid leukemia: Insight into genetic landscape and novel targeted approaches. in Biochemical Pharmacology. 2023;215:115705.
doi:10.1016/j.bcp.2023.115705 .

Tošic, Natasa, Marjanović, Irena, Lazić, Jelena, "Pediatric acute myeloid leukemia: Insight into genetic landscape and novel targeted approaches" in Biochemical Pharmacology, 215 (2023):115705,
https://doi.org/10.1016/j.bcp.2023.115705 . .

TY  - CONF
AU  - Virijević, Marijana
AU  - Marjanović, Irena
AU  - Anđelković, Marina
AU  - Vuković, Nada Suvajdžić
AU  - Jaković, Ljubomir
AU  - Micić, Dragan
AU  - Lalosević, Milica Stojković
AU  - Bogdanović, Andrija
AU  - Pavlović, Sonja
PY  - 2023
UR  - https://journals.lww.com/hemasphere/fulltext/2023/08003/pb2037__new_tert_variant_in_a_family_with_aplastic.1913.aspx
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/2156
AB  - Background:TERT gene, the most frequently mutated gene in patients with telomere biology disorders (telomeropathies), encode telomerase reverse transcriptase enzyme. Heterozygous variants in the TERT gene impair telomerase activity by haploinsufficiency and pathogenic variants are associated with bone marrow failure syndrome and acute myeloid leukemia predisposition. TERT variants show incomplete penetrance and can also be found in asymptomatic family members. Some patients with telomeropathies present with severe symptoms at early age, and in other diseases may appear later in life like aplastic anemia, pulmonary or hepatic fibrosis. Affected families may show anticipation that may result in more severe forms of the disease in succeeding generations. Due to the rarity of the disease and the small number of clinical trials, telomeropathies are often unrecognized and misdiagnosed.  Aims: To report a novel variant in TERT gene in familial hematopoietic disorder.  Methods: Next Generation Sequencing of DNA isolated from peripheral blood of a patient (older sister) with clinical diagnosis of aplastic anemia, using TruSight One MiSeq platform (Illumina®) and segregation sequencing analysis of patient’s mother and younger sister.  Results: We analyzed all three family members presented with a similar clinical appearance and hematology findings (moderate megaloblastic pancytopenia). Mother was diagnosed at age 14, but reevaluated before delivery in 2001 as hypoplastic MDS and trisomy 8 in karyotype with marked thrombocytopenia, being stable for years. Two daughters, both diagnosed as familiar aplastic anemia with normal karyotype, without elements of Fanconi anemia, at age of 13 and 14 yrs, also with profound thrombocytopenia without severe bleeding episodes. Moreover, lung and liver fibrosis were excluded. We identified a novel missense heterozygous variant c.2605G>A p.(Asp869Asn) in TERT gene in all three family members. This variant results in replacement of aspartic amino acid on 869 position in TERT enzyme polypeptide chain by asparagine. According to ACMG classification, detected variant is characterized as likely pathogenic, class 2. This variant is very rare and was detected in gnomAD exomes and gnomAD genomes data bases. It is located in highly conserved protein region and is very likely to disrupt the function of the enzyme.  Summary/Conclusion: As patients with telomeropathies often have a history of macrocytosis and mild to moderate thrombocytopenia, that can be wrongly diagnosed as immune-mediated thrombocytopenia, myelodysplastic syndrome or moderate aplastic anemia, our findings indicate that TERT rare variants pass under-recognized in these patients. Therefore, this report emphasizes the importance for routine deep genetics screening for TERT rare variants in patients with family history of cytopenia, different bone marrow failure syndromes and aplastic anemia, regardless the age or clinical presentation. This investigation is able to identify clinically inapparent telomere biology disorder and improve outcomes through forehand diagnosis setting, genetic counseling and the precise therapy considerations especially stem cell grafting.
C3  - HemaSphere
T1  - PB2037: NEW TERT VARIANT IN A FAMILY WITH APLASTIC ANEMIA
IS  - S3
SP  - e62401c5
VL  - 7
DO  - 10.1097/01.HS9.0000974956.62401.c5
ER  - 

@conference{
author = "Virijević, Marijana and Marjanović, Irena and Anđelković, Marina and Vuković, Nada Suvajdžić and Jaković, Ljubomir and Micić, Dragan and Lalosević, Milica Stojković and Bogdanović, Andrija and Pavlović, Sonja",
year = "2023",
abstract = "Background:TERT gene, the most frequently mutated gene in patients with telomere biology disorders (telomeropathies), encode telomerase reverse transcriptase enzyme. Heterozygous variants in the TERT gene impair telomerase activity by haploinsufficiency and pathogenic variants are associated with bone marrow failure syndrome and acute myeloid leukemia predisposition. TERT variants show incomplete penetrance and can also be found in asymptomatic family members. Some patients with telomeropathies present with severe symptoms at early age, and in other diseases may appear later in life like aplastic anemia, pulmonary or hepatic fibrosis. Affected families may show anticipation that may result in more severe forms of the disease in succeeding generations. Due to the rarity of the disease and the small number of clinical trials, telomeropathies are often unrecognized and misdiagnosed.  Aims: To report a novel variant in TERT gene in familial hematopoietic disorder.  Methods: Next Generation Sequencing of DNA isolated from peripheral blood of a patient (older sister) with clinical diagnosis of aplastic anemia, using TruSight One MiSeq platform (Illumina®) and segregation sequencing analysis of patient’s mother and younger sister.  Results: We analyzed all three family members presented with a similar clinical appearance and hematology findings (moderate megaloblastic pancytopenia). Mother was diagnosed at age 14, but reevaluated before delivery in 2001 as hypoplastic MDS and trisomy 8 in karyotype with marked thrombocytopenia, being stable for years. Two daughters, both diagnosed as familiar aplastic anemia with normal karyotype, without elements of Fanconi anemia, at age of 13 and 14 yrs, also with profound thrombocytopenia without severe bleeding episodes. Moreover, lung and liver fibrosis were excluded. We identified a novel missense heterozygous variant c.2605G>A p.(Asp869Asn) in TERT gene in all three family members. This variant results in replacement of aspartic amino acid on 869 position in TERT enzyme polypeptide chain by asparagine. According to ACMG classification, detected variant is characterized as likely pathogenic, class 2. This variant is very rare and was detected in gnomAD exomes and gnomAD genomes data bases. It is located in highly conserved protein region and is very likely to disrupt the function of the enzyme.  Summary/Conclusion: As patients with telomeropathies often have a history of macrocytosis and mild to moderate thrombocytopenia, that can be wrongly diagnosed as immune-mediated thrombocytopenia, myelodysplastic syndrome or moderate aplastic anemia, our findings indicate that TERT rare variants pass under-recognized in these patients. Therefore, this report emphasizes the importance for routine deep genetics screening for TERT rare variants in patients with family history of cytopenia, different bone marrow failure syndromes and aplastic anemia, regardless the age or clinical presentation. This investigation is able to identify clinically inapparent telomere biology disorder and improve outcomes through forehand diagnosis setting, genetic counseling and the precise therapy considerations especially stem cell grafting.",
journal = "HemaSphere",
title = "PB2037: NEW TERT VARIANT IN A FAMILY WITH APLASTIC ANEMIA",
number = "S3",
pages = "e62401c5",
volume = "7",
doi = "10.1097/01.HS9.0000974956.62401.c5"
}

Virijević, M., Marjanović, I., Anđelković, M., Vuković, N. S., Jaković, L., Micić, D., Lalosević, M. S., Bogdanović, A.,& Pavlović, S.. (2023). PB2037: NEW TERT VARIANT IN A FAMILY WITH APLASTIC ANEMIA. in HemaSphere, 7(S3), e62401c5.
https://doi.org/10.1097/01.HS9.0000974956.62401.c5

Virijević M, Marjanović I, Anđelković M, Vuković NS, Jaković L, Micić D, Lalosević MS, Bogdanović A, Pavlović S. PB2037: NEW TERT VARIANT IN A FAMILY WITH APLASTIC ANEMIA. in HemaSphere. 2023;7(S3):e62401c5.
doi:10.1097/01.HS9.0000974956.62401.c5 .

Virijević, Marijana, Marjanović, Irena, Anđelković, Marina, Vuković, Nada Suvajdžić, Jaković, Ljubomir, Micić, Dragan, Lalosević, Milica Stojković, Bogdanović, Andrija, Pavlović, Sonja, "PB2037: NEW TERT VARIANT IN A FAMILY WITH APLASTIC ANEMIA" in HemaSphere, 7, no. S3 (2023):e62401c5,
https://doi.org/10.1097/01.HS9.0000974956.62401.c5 . .

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  - 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  - 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  - 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  - 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  - THES
AU  - Marjanović, Irena
PY  - 2018
UR  - http://eteze.bg.ac.rs/application/showtheses?thesesId=5740
UR  - https://nardus.mpn.gov.rs/handle/123456789/9411
UR  - https://fedorabg.bg.ac.rs/fedora/get/o:17563/bdef:Content/download
UR  - http://vbs.rs/scripts/cobiss?command=DISPLAY&base=70036&RID=1025184690
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/48
AB  - Akutna mijeloidna leukemija (AML) predstavlja grupu hematoloških malignih oboljenja koju karakteriše heterogeni genetički i epigenetički profil. AML sa normalnim kariotipom (AML-NK) predstavlja najveću podgrupu u okviru AML, koju odlikuje intermedijarni rizik. Međutim, samo 40% obolelih od AML-NK preživljava duže od 5 godina, pa je neophodno otkriti molekularno-genetičke markere značajne za prognozu i praćenje toka bolesti, rano otkrivanje minimalne rezidualne bolesti (MRB) i izbor odgovarajuće terapije, kako bi bila omogućena bolja stratifikacija pacijenata sa AML-NK. Prvi cilj ove studije je analiza mutacionog profila dečje (dAML) i adultne (aAML) koja će doprineti rasvetljenju patogeneze mijeloidnih leukemija. Drugi cilj predstavlja određivanje nivoa ekspresije WT1, EVI1, BAALC i MN1 gena, kao potencijalnih molekularno-genetičkih markera značajnih za AML-NK. Analizirani su neselektovani DNK uzorci 20 dAML i 20 aAML pacijenata, primenom metode targetovanog sekvenciranja nove generacije (eng. „targeted next generation sequencing“ – NGS), TruSeq Amplicon - Cancer Panel (TSACP) esejem, koji omogućava detekciju somatskih mutacija u 48 gena uključenih u kancerogenezu. U drugom delu ove studije nivo ekspresije gena WT1 (104 pacijenta), EVI1 (104 pacijenta), BAALC (111 pacijenata) i MN1 (111 pacijenata) u mononuklearnim ćelijama koštane srži AML-NK pacijenata i zdravih pojedinaca analiziran je real-time PCR metodom. Rezultati su pokazali da AML sadrži relativno mali broj genetičkih promena, u proseku samo 3 mutacije po pacijentu kod aAML i dAML grupe pacijenata. Zastupljenost najčešćih mutacija u pojedinačnim genima, koji su povezani sa patogenezom AML, razlikovala se kod dAML i aAML: IDH1 (0% kod dAML, 5% kod aAML), IDH2 (0% kod dAML, 10% kod aAML), NPM1 (10% kod dAML, 35% kod aAML). Takođe, prisustvo mutacija u 4 gena (JAK3, ABL1, GNAQ i EGFR) koji kodiraju tirozin kinaze ili proteine koji su udruženi sa tirozin kinazama detektovano je isključivo kod dAML pacijenata, dok je kod 5 gena (IDH1, APC, HNF1A, GNAS i SMARCB1) koji su uključeni u metilaciju i modifikaciju histona prisustvo mutacija utvrđeno isključivo kod aAML pacijenata...
AB  - Acute myeloid leukemia (AML) is a group of haematological malignancies characterized by a heterogeneous genetic and epigenetic profile. AML with normal karyotype (AML-NK) represents the largest subgroup within the AML, characterized by an intermediate risk. However, only 40% of patients with AML-NK survive for more than 5 years, so it is necessary to detect molecular genetic markers significant for prognosis and disease monitoring, early detection of minimum residual disease (MRD), and the selection of appropriate therapy in order to enable better stratification of patients with AML-NK. The first aim of this study is the analysis of the mutation profile of childhood (cAML) and adult (aAML) AML which will contribute to the clarification of the pathogenesis of myeloid leukemia. The second aim is to determine the level of expression of WT1, EVI1, BAALC and MN1 gene, as potential molecular genetic markers relevant to AML-NK. Unselected DNA samples of 20 cAMLs and 20 aAML patients were analyzed using the targeted next generation sequencing (NGS) method, on the TruSeq Amplicon-Cancer Panel (TSACP), which enables the detection of somatic mutations in 48 genes involved in carcinogenesis. In the second part of this research, the level of expression of the genes WT1 (104 patients), EVI1 (104 patients), BAALC (111 patients) and MN1 (111 patients) was analyzed in mononuclear bone marrow cells of AML-NK patients and healthy individuals by the real-time PCR method. The results showed that the AML contains a relatively small number of genetic changes, on average only 3 mutations per patient in the aAML and cAML group. The incidence of the most common mutations in individual genes, which are associated with AML pathogenesis, differed in cAML and aAML: IDH1 (0% in cAML, 5% in aAML), IDH2 (0% in cAML, 10% in aAML), NPM1 (10% in cAML, 35% in aAML). Also, the presence of mutations in 4 genes (JAK3, ABL1, GNAQ, and EGFR) that encode tyrosine kinases or proteins that are associated with tyrosine kinases were detected exclusively in cAML patients, while in 5 genes (IDH1, APC, HNF1A, GNAS and SMARCB1) involved in methylation and histone modification, the presence of mutations was found exclusively in aAML patients...
PB  - Univerzitet u Beogradu, Biološki fakultet
T1  - Identifikacija molekularno-genetičkih markera patogeneze akutne mijeloidne leukemije
T1  - Identification of molecular genetic markers of acute myeloid leukemia pathogenesis
UR  - https://hdl.handle.net/21.15107/rcub_nardus_9411
ER  - 

@phdthesis{
author = "Marjanović, Irena",
year = "2018",
abstract = "Akutna mijeloidna leukemija (AML) predstavlja grupu hematoloških malignih oboljenja koju karakteriše heterogeni genetički i epigenetički profil. AML sa normalnim kariotipom (AML-NK) predstavlja najveću podgrupu u okviru AML, koju odlikuje intermedijarni rizik. Međutim, samo 40% obolelih od AML-NK preživljava duže od 5 godina, pa je neophodno otkriti molekularno-genetičke markere značajne za prognozu i praćenje toka bolesti, rano otkrivanje minimalne rezidualne bolesti (MRB) i izbor odgovarajuće terapije, kako bi bila omogućena bolja stratifikacija pacijenata sa AML-NK. Prvi cilj ove studije je analiza mutacionog profila dečje (dAML) i adultne (aAML) koja će doprineti rasvetljenju patogeneze mijeloidnih leukemija. Drugi cilj predstavlja određivanje nivoa ekspresije WT1, EVI1, BAALC i MN1 gena, kao potencijalnih molekularno-genetičkih markera značajnih za AML-NK. Analizirani su neselektovani DNK uzorci 20 dAML i 20 aAML pacijenata, primenom metode targetovanog sekvenciranja nove generacije (eng. „targeted next generation sequencing“ – NGS), TruSeq Amplicon - Cancer Panel (TSACP) esejem, koji omogućava detekciju somatskih mutacija u 48 gena uključenih u kancerogenezu. U drugom delu ove studije nivo ekspresije gena WT1 (104 pacijenta), EVI1 (104 pacijenta), BAALC (111 pacijenata) i MN1 (111 pacijenata) u mononuklearnim ćelijama koštane srži AML-NK pacijenata i zdravih pojedinaca analiziran je real-time PCR metodom. Rezultati su pokazali da AML sadrži relativno mali broj genetičkih promena, u proseku samo 3 mutacije po pacijentu kod aAML i dAML grupe pacijenata. Zastupljenost najčešćih mutacija u pojedinačnim genima, koji su povezani sa patogenezom AML, razlikovala se kod dAML i aAML: IDH1 (0% kod dAML, 5% kod aAML), IDH2 (0% kod dAML, 10% kod aAML), NPM1 (10% kod dAML, 35% kod aAML). Takođe, prisustvo mutacija u 4 gena (JAK3, ABL1, GNAQ i EGFR) koji kodiraju tirozin kinaze ili proteine koji su udruženi sa tirozin kinazama detektovano je isključivo kod dAML pacijenata, dok je kod 5 gena (IDH1, APC, HNF1A, GNAS i SMARCB1) koji su uključeni u metilaciju i modifikaciju histona prisustvo mutacija utvrđeno isključivo kod aAML pacijenata..., Acute myeloid leukemia (AML) is a group of haematological malignancies characterized by a heterogeneous genetic and epigenetic profile. AML with normal karyotype (AML-NK) represents the largest subgroup within the AML, characterized by an intermediate risk. However, only 40% of patients with AML-NK survive for more than 5 years, so it is necessary to detect molecular genetic markers significant for prognosis and disease monitoring, early detection of minimum residual disease (MRD), and the selection of appropriate therapy in order to enable better stratification of patients with AML-NK. The first aim of this study is the analysis of the mutation profile of childhood (cAML) and adult (aAML) AML which will contribute to the clarification of the pathogenesis of myeloid leukemia. The second aim is to determine the level of expression of WT1, EVI1, BAALC and MN1 gene, as potential molecular genetic markers relevant to AML-NK. Unselected DNA samples of 20 cAMLs and 20 aAML patients were analyzed using the targeted next generation sequencing (NGS) method, on the TruSeq Amplicon-Cancer Panel (TSACP), which enables the detection of somatic mutations in 48 genes involved in carcinogenesis. In the second part of this research, the level of expression of the genes WT1 (104 patients), EVI1 (104 patients), BAALC (111 patients) and MN1 (111 patients) was analyzed in mononuclear bone marrow cells of AML-NK patients and healthy individuals by the real-time PCR method. The results showed that the AML contains a relatively small number of genetic changes, on average only 3 mutations per patient in the aAML and cAML group. The incidence of the most common mutations in individual genes, which are associated with AML pathogenesis, differed in cAML and aAML: IDH1 (0% in cAML, 5% in aAML), IDH2 (0% in cAML, 10% in aAML), NPM1 (10% in cAML, 35% in aAML). Also, the presence of mutations in 4 genes (JAK3, ABL1, GNAQ, and EGFR) that encode tyrosine kinases or proteins that are associated with tyrosine kinases were detected exclusively in cAML patients, while in 5 genes (IDH1, APC, HNF1A, GNAS and SMARCB1) involved in methylation and histone modification, the presence of mutations was found exclusively in aAML patients...",
publisher = "Univerzitet u Beogradu, Biološki fakultet",
title = "Identifikacija molekularno-genetičkih markera patogeneze akutne mijeloidne leukemije, Identification of molecular genetic markers of acute myeloid leukemia pathogenesis",
url = "https://hdl.handle.net/21.15107/rcub_nardus_9411"
}

Marjanović, I.. (2018). Identifikacija molekularno-genetičkih markera patogeneze akutne mijeloidne leukemije. 
Univerzitet u Beogradu, Biološki fakultet..
https://hdl.handle.net/21.15107/rcub_nardus_9411

Marjanović I. Identifikacija molekularno-genetičkih markera patogeneze akutne mijeloidne leukemije. 2018;.
https://hdl.handle.net/21.15107/rcub_nardus_9411 .

Marjanović, Irena, "Identifikacija molekularno-genetičkih markera patogeneze akutne mijeloidne leukemije" (2018),
https://hdl.handle.net/21.15107/rcub_nardus_9411 .

TY  - JOUR
AU  - Marjanović, Irena
AU  - Karan-Đurašević, Teodora
AU  - Ugrin, Milena
AU  - Virijević, Marijana
AU  - Vidović, Ana
AU  - Tomin, Dragica
AU  - Suvajdžić-Vuković, Nada
AU  - Pavlović, Sonja
AU  - Tošić, Nataša
PY  - 2017
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/1089
AB  - The aim of the present study was to test the possibility for the usage of the WT1 (Wilms tumor 1) expression level as an additional biomarker for prognosis and minimal residual disease (MRD) monitoring in patients with acute myeloid leukemia with normal karyotype (AML-NK). We found that overexpression of WT1 had a negative effect on treatment outcome. It was a suitable marker for MRD monitoring and a marker for refined risk stratification of AML-NK patients. Background: Acute myeloid leukemia with normal karyotype (AML-NK) represents the largest group of AML patients classified with an intermediate prognosis. A constant need exists to introduce new molecular markers for more precise risk stratification and for minimal residual disease (MRD) monitoring. Patients and Methods: Quantitative assessment of Wilms tumor 1 (WT1) gene transcripts was performed using real-time polymerase chain reaction. The bone marrow samples were collected at the diagnosis from 104 AML-NK patients and from 34 of these patients during follow-up or disease relapse. Results: We found that overexpression of the WT1 gene (WT1(high) status), present in 25.5% of patients, was an independent unfavorable factor for achieving complete remission. WT1(high) status was also associated with resistance to therapy and shorter disease-free survival and overall survival. Assessment of the log reduction value of WT1 expression, measured in paired diagnosis/complete remission samples, revealed that patients with a log reduction of  lt  2 had a tendency toward shorter disease-free survival and overall survival and a greater incidence of disease relapse. Combining WT1 gene expression status with NPM1 and FLT3-ITD mutational status, we found that the tumor behavior of intermediate patients (FLT3(-)ITD-/NPM1(-) double negative) with WT1(high) status is almost the same as the tumor behavior of the adverse risk group. Conclusion: WT1 expression status represents a good molecular marker of prognosis, response to treatment, and MRD monitoring. Above all, the usage of the WT1 expression level as an additional marker for more precise risk stratification of AML-NK patients could lead to more adapted, personalized treatment protocols.
PB  - CIG Media Group, Lp, Dallas
T2  - Clinical Lymphoma Myeloma & Leukemia
T1  - Use of Wilms Tumor 1 Gene Expression as a Reliable Marker for Prognosis and Minimal Residual Disease Monitoring in Acute Myeloid Leukemia With Normal Karyotype Patients
EP  - 319
IS  - 5
SP  - 312
VL  - 17
DO  - 10.1016/j.clml.2016.12.006
ER  - 

@article{
author = "Marjanović, Irena and Karan-Đurašević, Teodora and Ugrin, Milena and Virijević, Marijana and Vidović, Ana and Tomin, Dragica and Suvajdžić-Vuković, Nada and Pavlović, Sonja and Tošić, Nataša",
year = "2017",
abstract = "The aim of the present study was to test the possibility for the usage of the WT1 (Wilms tumor 1) expression level as an additional biomarker for prognosis and minimal residual disease (MRD) monitoring in patients with acute myeloid leukemia with normal karyotype (AML-NK). We found that overexpression of WT1 had a negative effect on treatment outcome. It was a suitable marker for MRD monitoring and a marker for refined risk stratification of AML-NK patients. Background: Acute myeloid leukemia with normal karyotype (AML-NK) represents the largest group of AML patients classified with an intermediate prognosis. A constant need exists to introduce new molecular markers for more precise risk stratification and for minimal residual disease (MRD) monitoring. Patients and Methods: Quantitative assessment of Wilms tumor 1 (WT1) gene transcripts was performed using real-time polymerase chain reaction. The bone marrow samples were collected at the diagnosis from 104 AML-NK patients and from 34 of these patients during follow-up or disease relapse. Results: We found that overexpression of the WT1 gene (WT1(high) status), present in 25.5% of patients, was an independent unfavorable factor for achieving complete remission. WT1(high) status was also associated with resistance to therapy and shorter disease-free survival and overall survival. Assessment of the log reduction value of WT1 expression, measured in paired diagnosis/complete remission samples, revealed that patients with a log reduction of  lt  2 had a tendency toward shorter disease-free survival and overall survival and a greater incidence of disease relapse. Combining WT1 gene expression status with NPM1 and FLT3-ITD mutational status, we found that the tumor behavior of intermediate patients (FLT3(-)ITD-/NPM1(-) double negative) with WT1(high) status is almost the same as the tumor behavior of the adverse risk group. Conclusion: WT1 expression status represents a good molecular marker of prognosis, response to treatment, and MRD monitoring. Above all, the usage of the WT1 expression level as an additional marker for more precise risk stratification of AML-NK patients could lead to more adapted, personalized treatment protocols.",
publisher = "CIG Media Group, Lp, Dallas",
journal = "Clinical Lymphoma Myeloma & Leukemia",
title = "Use of Wilms Tumor 1 Gene Expression as a Reliable Marker for Prognosis and Minimal Residual Disease Monitoring in Acute Myeloid Leukemia With Normal Karyotype Patients",
pages = "319-312",
number = "5",
volume = "17",
doi = "10.1016/j.clml.2016.12.006"
}

Marjanović, I., Karan-Đurašević, T., Ugrin, M., Virijević, M., Vidović, A., Tomin, D., Suvajdžić-Vuković, N., Pavlović, S.,& Tošić, N.. (2017). Use of Wilms Tumor 1 Gene Expression as a Reliable Marker for Prognosis and Minimal Residual Disease Monitoring in Acute Myeloid Leukemia With Normal Karyotype Patients. in Clinical Lymphoma Myeloma & Leukemia
CIG Media Group, Lp, Dallas., 17(5), 312-319.
https://doi.org/10.1016/j.clml.2016.12.006

Marjanović I, Karan-Đurašević T, Ugrin M, Virijević M, Vidović A, Tomin D, Suvajdžić-Vuković N, Pavlović S, Tošić N. Use of Wilms Tumor 1 Gene Expression as a Reliable Marker for Prognosis and Minimal Residual Disease Monitoring in Acute Myeloid Leukemia With Normal Karyotype Patients. in Clinical Lymphoma Myeloma & Leukemia. 2017;17(5):312-319.
doi:10.1016/j.clml.2016.12.006 .

Marjanović, Irena, Karan-Đurašević, Teodora, Ugrin, Milena, Virijević, Marijana, Vidović, Ana, Tomin, Dragica, Suvajdžić-Vuković, Nada, Pavlović, Sonja, Tošić, Nataša, "Use of Wilms Tumor 1 Gene Expression as a Reliable Marker for Prognosis and Minimal Residual Disease Monitoring in Acute Myeloid Leukemia With Normal Karyotype Patients" in Clinical Lymphoma Myeloma & Leukemia, 17, no. 5 (2017):312-319,
https://doi.org/10.1016/j.clml.2016.12.006 . .

TY  - CONF
AU  - Perić, Jelena
AU  - Karan-Đurašević, Teodora
AU  - Kostić, Tatjana 
AU  - Marjanović, Irena
AU  - Lazić, J.
AU  - Virijević, M.
AU  - Krstovski, N.
AU  - Dokmanović, Lidija
AU  - Tomin, D.
AU  - Vidović, A.
AU  - Suvajdžić-Vuković, Nada
AU  - Janić, D.
AU  - Pavlović, Sonja
AU  - Tošić, Nataša
PY  - 2017
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/1071
PB  - Ferrata Storti Foundation, Pavia
C3  - Haematologica-The Hematology Journal
T1  - Targeted mutational profiling of childhood and adult acute lymphoblastic leukemia patients
EP  - 653
SP  - 653
VL  - 102
UR  - https://hdl.handle.net/21.15107/rcub_imagine_1071
ER  - 

@conference{
author = "Perić, Jelena and Karan-Đurašević, Teodora and Kostić, Tatjana  and Marjanović, Irena and Lazić, J. and Virijević, M. and Krstovski, N. and Dokmanović, Lidija and Tomin, D. and Vidović, A. and Suvajdžić-Vuković, Nada and Janić, D. and Pavlović, Sonja and Tošić, Nataša",
year = "2017",
publisher = "Ferrata Storti Foundation, Pavia",
journal = "Haematologica-The Hematology Journal",
title = "Targeted mutational profiling of childhood and adult acute lymphoblastic leukemia patients",
pages = "653-653",
volume = "102",
url = "https://hdl.handle.net/21.15107/rcub_imagine_1071"
}

Perić, J., Karan-Đurašević, T., Kostić, T., Marjanović, I., Lazić, J., Virijević, M., Krstovski, N., Dokmanović, L., Tomin, D., Vidović, A., Suvajdžić-Vuković, N., Janić, D., Pavlović, S.,& Tošić, N.. (2017). Targeted mutational profiling of childhood and adult acute lymphoblastic leukemia patients. in Haematologica-The Hematology Journal
Ferrata Storti Foundation, Pavia., 102, 653-653.
https://hdl.handle.net/21.15107/rcub_imagine_1071

Perić J, Karan-Đurašević T, Kostić T, Marjanović I, Lazić J, Virijević M, Krstovski N, Dokmanović L, Tomin D, Vidović A, Suvajdžić-Vuković N, Janić D, Pavlović S, Tošić N. Targeted mutational profiling of childhood and adult acute lymphoblastic leukemia patients. in Haematologica-The Hematology Journal. 2017;102:653-653.
https://hdl.handle.net/21.15107/rcub_imagine_1071 .

Perić, Jelena, Karan-Đurašević, Teodora, Kostić, Tatjana , Marjanović, Irena, Lazić, J., Virijević, M., Krstovski, N., Dokmanović, Lidija, Tomin, D., Vidović, A., Suvajdžić-Vuković, Nada, Janić, D., Pavlović, Sonja, Tošić, Nataša, "Targeted mutational profiling of childhood and adult acute lymphoblastic leukemia patients" in Haematologica-The Hematology Journal, 102 (2017):653-653,
https://hdl.handle.net/21.15107/rcub_imagine_1071 .

TY  - JOUR
AU  - Janković, Srdja
AU  - Marjanović, Irena
AU  - Tošić, Nataša
AU  - Kotur, Nikola
AU  - Dokmanović, Lidija
AU  - Skorić, Dejan
AU  - Krstovski, Nada
AU  - Lazić, Jelena
AU  - Rodić, Predrag
AU  - Pavlović, Sonja
AU  - Janić, Dragana
PY  - 2016
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/946
AB  - Acute leukemias constitute the most common malignancy in childhood, accounting for 25-35% of all cancer in children. They are divided into acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML). Genetic susceptibility is known to play a major role in childhood leukemias. Wilms tumor (WT)1 is a zinc finger transcription factor involved in regulating the process of cell differentiation; it has been implicated in a wide range of human neoplasms. WT1 overexpression in the bone marrow at diagnosis is reported to be an independent negative prognostic factor in adults and children with AML. The aim of the present investigation was to determine the expression of WT1 in the bone marrow of children with AML and ALL in Serbia and its possible impact on patient survival. We determined bone marrow WT1 expression levels by reverse -transcription polymerase chain reaction (RT-PCR) at diagnosis in 20 children with AML and 20 children with ALL (16 B-ALL and 4 T-ALL), as well as 15 age- and sex-matched controls who were evaluated for immune thrombocytopenic purpura (ITP). For children with AML, follow-up samples were also analyzed one month after treatment initiation and at variable later timepoints of control punctures. The results were normalized based on WT1 expression in controls. We found that children with AML had significantly higher WT1 expression at diagnosis (median SD: 139.42 244.03) than those with ALL (1.18 54.37; Mann -Whitney U=82; p lt 0.01) and ITP (0.76 1.01; U=32; p lt 0.01). Patients with T-ALL had higher WT1 expression than those with B-ALL, though significance was not reached due to subgroup size; differences between AML subgroups according to the French-American-British (FAB) classification were also below the level of significance, though a tendency toward higher values in M3 and M4 leukemias was notable. There was also a tendency toward higher values in 14 children with AML who were still alive after a median follow-up of 1.5 years (181.42 192.52) than in 6 who succumbed to the disease (104.29 354.87). All children with AML who had WT1 expression 1 month after diagnosis below the fourth quartile (10 of 10) were still alive, while only 2 of 5 with 1 -month WT1 expression in the fourth quartile survived (Fisher's exact test: p=0.0952). Taken together, our results support a role for WT1 in the diagnostic workup in children with acute leukemia, although it needs to be considered in view of a complex and indvidualized context.
PB  - Društvo genetičara Srbije, Beograd
T2  - Genetika-Belgrade
T1  - Wilms tumor (wt)1 gene expression in children with acute leukemia in Serbia
EP  - 421
IS  - 1
SP  - 409
VL  - 48
DO  - 10.2298/GENSR1601409J
ER  - 

@article{
author = "Janković, Srdja and Marjanović, Irena and Tošić, Nataša and Kotur, Nikola and Dokmanović, Lidija and Skorić, Dejan and Krstovski, Nada and Lazić, Jelena and Rodić, Predrag and Pavlović, Sonja and Janić, Dragana",
year = "2016",
abstract = "Acute leukemias constitute the most common malignancy in childhood, accounting for 25-35% of all cancer in children. They are divided into acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML). Genetic susceptibility is known to play a major role in childhood leukemias. Wilms tumor (WT)1 is a zinc finger transcription factor involved in regulating the process of cell differentiation; it has been implicated in a wide range of human neoplasms. WT1 overexpression in the bone marrow at diagnosis is reported to be an independent negative prognostic factor in adults and children with AML. The aim of the present investigation was to determine the expression of WT1 in the bone marrow of children with AML and ALL in Serbia and its possible impact on patient survival. We determined bone marrow WT1 expression levels by reverse -transcription polymerase chain reaction (RT-PCR) at diagnosis in 20 children with AML and 20 children with ALL (16 B-ALL and 4 T-ALL), as well as 15 age- and sex-matched controls who were evaluated for immune thrombocytopenic purpura (ITP). For children with AML, follow-up samples were also analyzed one month after treatment initiation and at variable later timepoints of control punctures. The results were normalized based on WT1 expression in controls. We found that children with AML had significantly higher WT1 expression at diagnosis (median SD: 139.42 244.03) than those with ALL (1.18 54.37; Mann -Whitney U=82; p lt 0.01) and ITP (0.76 1.01; U=32; p lt 0.01). Patients with T-ALL had higher WT1 expression than those with B-ALL, though significance was not reached due to subgroup size; differences between AML subgroups according to the French-American-British (FAB) classification were also below the level of significance, though a tendency toward higher values in M3 and M4 leukemias was notable. There was also a tendency toward higher values in 14 children with AML who were still alive after a median follow-up of 1.5 years (181.42 192.52) than in 6 who succumbed to the disease (104.29 354.87). All children with AML who had WT1 expression 1 month after diagnosis below the fourth quartile (10 of 10) were still alive, while only 2 of 5 with 1 -month WT1 expression in the fourth quartile survived (Fisher's exact test: p=0.0952). Taken together, our results support a role for WT1 in the diagnostic workup in children with acute leukemia, although it needs to be considered in view of a complex and indvidualized context.",
publisher = "Društvo genetičara Srbije, Beograd",
journal = "Genetika-Belgrade",
title = "Wilms tumor (wt)1 gene expression in children with acute leukemia in Serbia",
pages = "421-409",
number = "1",
volume = "48",
doi = "10.2298/GENSR1601409J"
}

Janković, S., Marjanović, I., Tošić, N., Kotur, N., Dokmanović, L., Skorić, D., Krstovski, N., Lazić, J., Rodić, P., Pavlović, S.,& Janić, D.. (2016). Wilms tumor (wt)1 gene expression in children with acute leukemia in Serbia. in Genetika-Belgrade
Društvo genetičara Srbije, Beograd., 48(1), 409-421.
https://doi.org/10.2298/GENSR1601409J

Janković S, Marjanović I, Tošić N, Kotur N, Dokmanović L, Skorić D, Krstovski N, Lazić J, Rodić P, Pavlović S, Janić D. Wilms tumor (wt)1 gene expression in children with acute leukemia in Serbia. in Genetika-Belgrade. 2016;48(1):409-421.
doi:10.2298/GENSR1601409J .

Janković, Srdja, Marjanović, Irena, Tošić, Nataša, Kotur, Nikola, Dokmanović, Lidija, Skorić, Dejan, Krstovski, Nada, Lazić, Jelena, Rodić, Predrag, Pavlović, Sonja, Janić, Dragana, "Wilms tumor (wt)1 gene expression in children with acute leukemia in Serbia" in Genetika-Belgrade, 48, no. 1 (2016):409-421,
https://doi.org/10.2298/GENSR1601409J . .

TY  - JOUR
AU  - Vučićević, Ksenija
AU  - Jakovljević, Vladimir
AU  - Čolović, Nataša
AU  - Tošić, Nataša
AU  - Kostić, Tatjana
AU  - Glumac, Irena
AU  - Pavlović, Sonja
AU  - Karan-Đurašević, Teodora
AU  - Čolović, Milica
PY  - 2016
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/982
AB  - Uvod: Rezistencija na apoptozu koja karakteriše maligne B limfocite in vivo u hroničnoj limfocitnoj leukemiji (HLL) delimično je uzrokovana unutrašnjim poremecajima apoptotske mašinerije u ovim celijama. Ti poremecaji su rezultat genetičkih promena i aberantne ekspresije regulatora procesa apoptoze, među kojima ključnu ulogu imaju članovi Bcl2 familije. Cilj: Cilj ove studije je bio da se ispita udruženost nivoa ekspresije proapoptotskog Bax gena, kao i Bcl2/Bax odnosa, sa kliničkim karakteristikama bolesnika sa HLL kao i molekularnim prognostičkim markerima, i to mutacionim statusom rearanžiranih gena za teške lance imunoglobulina (IGHV) i ekspresijom gena za lipoproteinsku lipazu (LPL). Metode: Analizirana je ekspresija Bax iRNK i Bcl2/Bax iRNK odnos u mononuklearnim celijama periferne krvi 58 bolesnika sa HLL i 10 zdravih kontrola metodom reverzne transkripcije i lančane reakcije polimeraze u realnom vremenu (qRT-PCR). Rezultati: Detektovana je povišena ekspresija Bax gena u HLL uzorcima u odnosu na kontrolne uzorke (p=0,003), kao i povišen Bcl2/Bax odnos (p= lt 0,001). Kada je u pitanju udruženost sa prognostičkim markerima, Bcl2/Bax odnos je ispoljio negativnu korelaciju sa vremenom udvostručavanja broja limfocita (r=-0,307; p=0,0451), dok je visoka ekspresija Bax bila povezana sa LPL-pozitivnim statusom (p=0,035). I ekspresija Bax gena i Bcl2/Bax odnos su bili viši kod bolesnika sa nemutiranim u odnosu na bolesnike sa mutiranim IGHV genima, ali nije dostignuta statistička značajnost. Zaključak: Rezultati ove studije ukazuju na mogucu ulogu poremecene ekspresije Bcl2 i Bax gena, koja dovodi do visokog Bcl2/Bax odnosa u leukemijskim celijama, u patogenezi i kliničkom toku HLL.
AB  - Background: In chronic lymphocytic leukemia (CLL), in vivo apoptotic resistance of malignant B lymphocytes results, in part, from the intrinsic defects of their apoptotic machinery. These include genetic alterations and aberrant expression of many apoptosis regulators, among which the Bcl2 family members play a central role. Aim: The aim of this study was to investigate the association of pro-apoptotic Bax gene expression and Bcl2/Bax ratio with the clinical features of CLL patients as well as with molecular prognostic markers, namely the mutational status of rearranged immunoglobulin heavy variable (IGHV) genes and lipoprotein lipase (LPL) gene expression. Methods: We analyzed the expression of Bax mRNA and Bcl2/Bax mRNA ratio in the peripheral blood mononuclear cells of 58 unselected CLL patients and 10 healthy controls by the quantitative reverse-transcriptase polymerase chain reaction. Results: We detected significant Bax gene overexpression in CLL samples compared to non-leukemic samples (p=0.003), as well as an elevated Bcl2/Bax ratio (p= lt 0.001). Regarding the association with prognostic markers, the Bcl2/Bax ratio showed a negative correlation to lymphocyte doubling time (r=-0.307; p=0.0451), while high-level Bax expression was associated with LPL-positive status (p=0.035). Both the expression of Bax and Bcl2/Bax ratio were higher in patients with unmutated vs. mutated IGHV rearrangements, but this difference did not reach statistical significance. Conclusions: Our results suggest that dysregulated expression of Bcl2 and Bax, which leads to a high Bcl2/Bax ratio in leukemic cells, contributes to the pathogenesis and clinical course of CLL.
PB  - Društvo medicinskih biohemičara Srbije, Beograd i Versita
T2  - Journal of Medical Biochemistry
T1  - Udruženost ekspresije Bax gena i Bcl2/Bax odnosa sa kliničkim i molekularnim prognostičkim markerima u hroničnoj limfocitnoj leukemiji
T1  - Association of Bax expression and Bcl2/Bax ratio with clinical and molecular prognostic markers in chronic lymphocytic leukemia
EP  - 157
IS  - 2
SP  - 150
VL  - 35
DO  - 10.1515/jomb-2015-0017
ER  - 

@article{
author = "Vučićević, Ksenija and Jakovljević, Vladimir and Čolović, Nataša and Tošić, Nataša and Kostić, Tatjana and Glumac, Irena and Pavlović, Sonja and Karan-Đurašević, Teodora and Čolović, Milica",
year = "2016",
abstract = "Uvod: Rezistencija na apoptozu koja karakteriše maligne B limfocite in vivo u hroničnoj limfocitnoj leukemiji (HLL) delimično je uzrokovana unutrašnjim poremecajima apoptotske mašinerije u ovim celijama. Ti poremecaji su rezultat genetičkih promena i aberantne ekspresije regulatora procesa apoptoze, među kojima ključnu ulogu imaju članovi Bcl2 familije. Cilj: Cilj ove studije je bio da se ispita udruženost nivoa ekspresije proapoptotskog Bax gena, kao i Bcl2/Bax odnosa, sa kliničkim karakteristikama bolesnika sa HLL kao i molekularnim prognostičkim markerima, i to mutacionim statusom rearanžiranih gena za teške lance imunoglobulina (IGHV) i ekspresijom gena za lipoproteinsku lipazu (LPL). Metode: Analizirana je ekspresija Bax iRNK i Bcl2/Bax iRNK odnos u mononuklearnim celijama periferne krvi 58 bolesnika sa HLL i 10 zdravih kontrola metodom reverzne transkripcije i lančane reakcije polimeraze u realnom vremenu (qRT-PCR). Rezultati: Detektovana je povišena ekspresija Bax gena u HLL uzorcima u odnosu na kontrolne uzorke (p=0,003), kao i povišen Bcl2/Bax odnos (p= lt 0,001). Kada je u pitanju udruženost sa prognostičkim markerima, Bcl2/Bax odnos je ispoljio negativnu korelaciju sa vremenom udvostručavanja broja limfocita (r=-0,307; p=0,0451), dok je visoka ekspresija Bax bila povezana sa LPL-pozitivnim statusom (p=0,035). I ekspresija Bax gena i Bcl2/Bax odnos su bili viši kod bolesnika sa nemutiranim u odnosu na bolesnike sa mutiranim IGHV genima, ali nije dostignuta statistička značajnost. Zaključak: Rezultati ove studije ukazuju na mogucu ulogu poremecene ekspresije Bcl2 i Bax gena, koja dovodi do visokog Bcl2/Bax odnosa u leukemijskim celijama, u patogenezi i kliničkom toku HLL., Background: In chronic lymphocytic leukemia (CLL), in vivo apoptotic resistance of malignant B lymphocytes results, in part, from the intrinsic defects of their apoptotic machinery. These include genetic alterations and aberrant expression of many apoptosis regulators, among which the Bcl2 family members play a central role. Aim: The aim of this study was to investigate the association of pro-apoptotic Bax gene expression and Bcl2/Bax ratio with the clinical features of CLL patients as well as with molecular prognostic markers, namely the mutational status of rearranged immunoglobulin heavy variable (IGHV) genes and lipoprotein lipase (LPL) gene expression. Methods: We analyzed the expression of Bax mRNA and Bcl2/Bax mRNA ratio in the peripheral blood mononuclear cells of 58 unselected CLL patients and 10 healthy controls by the quantitative reverse-transcriptase polymerase chain reaction. Results: We detected significant Bax gene overexpression in CLL samples compared to non-leukemic samples (p=0.003), as well as an elevated Bcl2/Bax ratio (p= lt 0.001). Regarding the association with prognostic markers, the Bcl2/Bax ratio showed a negative correlation to lymphocyte doubling time (r=-0.307; p=0.0451), while high-level Bax expression was associated with LPL-positive status (p=0.035). Both the expression of Bax and Bcl2/Bax ratio were higher in patients with unmutated vs. mutated IGHV rearrangements, but this difference did not reach statistical significance. Conclusions: Our results suggest that dysregulated expression of Bcl2 and Bax, which leads to a high Bcl2/Bax ratio in leukemic cells, contributes to the pathogenesis and clinical course of CLL.",
publisher = "Društvo medicinskih biohemičara Srbije, Beograd i Versita",
journal = "Journal of Medical Biochemistry",
title = "Udruženost ekspresije Bax gena i Bcl2/Bax odnosa sa kliničkim i molekularnim prognostičkim markerima u hroničnoj limfocitnoj leukemiji, Association of Bax expression and Bcl2/Bax ratio with clinical and molecular prognostic markers in chronic lymphocytic leukemia",
pages = "157-150",
number = "2",
volume = "35",
doi = "10.1515/jomb-2015-0017"
}

Vučićević, K., Jakovljević, V., Čolović, N., Tošić, N., Kostić, T., Glumac, I., Pavlović, S., Karan-Đurašević, T.,& Čolović, M.. (2016). Udruženost ekspresije Bax gena i Bcl2/Bax odnosa sa kliničkim i molekularnim prognostičkim markerima u hroničnoj limfocitnoj leukemiji. in Journal of Medical Biochemistry
Društvo medicinskih biohemičara Srbije, Beograd i Versita., 35(2), 150-157.
https://doi.org/10.1515/jomb-2015-0017

Vučićević K, Jakovljević V, Čolović N, Tošić N, Kostić T, Glumac I, Pavlović S, Karan-Đurašević T, Čolović M. Udruženost ekspresije Bax gena i Bcl2/Bax odnosa sa kliničkim i molekularnim prognostičkim markerima u hroničnoj limfocitnoj leukemiji. in Journal of Medical Biochemistry. 2016;35(2):150-157.
doi:10.1515/jomb-2015-0017 .

Vučićević, Ksenija, Jakovljević, Vladimir, Čolović, Nataša, Tošić, Nataša, Kostić, Tatjana, Glumac, Irena, Pavlović, Sonja, Karan-Đurašević, Teodora, Čolović, Milica, "Udruženost ekspresije Bax gena i Bcl2/Bax odnosa sa kliničkim i molekularnim prognostičkim markerima u hroničnoj limfocitnoj leukemiji" in Journal of Medical Biochemistry, 35, no. 2 (2016):150-157,
https://doi.org/10.1515/jomb-2015-0017 . .

TY  - JOUR
AU  - Marjanović, Irena
AU  - Perić, Jelena
AU  - Stanić, Bojana
AU  - Pejanović, Nadja
AU  - Lucić, Bojana
AU  - Karan-Đurašević, Teodora
AU  - Janić, Dragana
AU  - Dokmanović, Lidija
AU  - Janković, Srdja
AU  - Suvajdžić-Vuković, Nada
AU  - Tomin, Dragica
AU  - Perisić, Ognjen
AU  - Rakocević, Goran
AU  - Popović, Milos
AU  - Pavlović, Sonja
AU  - Tošić, Nataša
PY  - 2016
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/932
AB  - The age-specific differences in the genetic mechanisms of myeloid leukemogenesis have been observed and studied previously. However, NGS technology has provided a possibility to obtain a large amount of mutation data. We analyzed DNA samples from 20 childhood (cAML) and 20 adult AML (aAML) patients, using NGS targeted sequencing. The average coverage of high-quality sequences was 2981 x per amplicon. A total of 412 (207 cAML, 205 aAML) variants in the coding regions were detected; out of which, only 122 (62 cAML and 60 aAML) were potentially protein-changing. Our results confirmed that AML contains small number of genetic alterations (median 3 mutations/patient in both groups). The prevalence of the most frequent single gene AML associated mutations differed in cAML and aAML patient cohorts: IDH1 (0 % cAML, 5 % aAML), IDH2 (0 % cAML, 10 % aAML), NPM1 (10 % cAML, 35 % aAML). Additionally, potentially protein-changing variants were found in tyrosine kinase genes or genes encoding tyrosine kinase associated proteins (JAK3, ABL1, GNAQ, and EGFR) in cAML, while among aAML, the prevalence is directed towards variants in the methylation and histone modifying genes (IDH1, IDH2, and SMARCB1). Besides uniform genomic profile of AML, specific genetic characteristic was exclusively detected in cAML and aAML.
PB  - Sage Publications Ltd, London
T2  - Tumor Biology
T1  - Parallel targeted next generation sequencing of childhood and adult acute myeloid leukemia patients reveals uniform genomic profile of the disease
EP  - 13401
IS  - 10
SP  - 13391
VL  - 37
DO  - 10.1007/s13277-016-5142-7
ER  - 

@article{
author = "Marjanović, Irena and Perić, Jelena and Stanić, Bojana and Pejanović, Nadja and Lucić, Bojana and Karan-Đurašević, Teodora and Janić, Dragana and Dokmanović, Lidija and Janković, Srdja and Suvajdžić-Vuković, Nada and Tomin, Dragica and Perisić, Ognjen and Rakocević, Goran and Popović, Milos and Pavlović, Sonja and Tošić, Nataša",
year = "2016",
abstract = "The age-specific differences in the genetic mechanisms of myeloid leukemogenesis have been observed and studied previously. However, NGS technology has provided a possibility to obtain a large amount of mutation data. We analyzed DNA samples from 20 childhood (cAML) and 20 adult AML (aAML) patients, using NGS targeted sequencing. The average coverage of high-quality sequences was 2981 x per amplicon. A total of 412 (207 cAML, 205 aAML) variants in the coding regions were detected; out of which, only 122 (62 cAML and 60 aAML) were potentially protein-changing. Our results confirmed that AML contains small number of genetic alterations (median 3 mutations/patient in both groups). The prevalence of the most frequent single gene AML associated mutations differed in cAML and aAML patient cohorts: IDH1 (0 % cAML, 5 % aAML), IDH2 (0 % cAML, 10 % aAML), NPM1 (10 % cAML, 35 % aAML). Additionally, potentially protein-changing variants were found in tyrosine kinase genes or genes encoding tyrosine kinase associated proteins (JAK3, ABL1, GNAQ, and EGFR) in cAML, while among aAML, the prevalence is directed towards variants in the methylation and histone modifying genes (IDH1, IDH2, and SMARCB1). Besides uniform genomic profile of AML, specific genetic characteristic was exclusively detected in cAML and aAML.",
publisher = "Sage Publications Ltd, London",
journal = "Tumor Biology",
title = "Parallel targeted next generation sequencing of childhood and adult acute myeloid leukemia patients reveals uniform genomic profile of the disease",
pages = "13401-13391",
number = "10",
volume = "37",
doi = "10.1007/s13277-016-5142-7"
}

Marjanović, I., Perić, J., Stanić, B., Pejanović, N., Lucić, B., Karan-Đurašević, T., Janić, D., Dokmanović, L., Janković, S., Suvajdžić-Vuković, N., Tomin, D., Perisić, O., Rakocević, G., Popović, M., Pavlović, S.,& Tošić, N.. (2016). Parallel targeted next generation sequencing of childhood and adult acute myeloid leukemia patients reveals uniform genomic profile of the disease. in Tumor Biology
Sage Publications Ltd, London., 37(10), 13391-13401.
https://doi.org/10.1007/s13277-016-5142-7

Marjanović I, Perić J, Stanić B, Pejanović N, Lucić B, Karan-Đurašević T, Janić D, Dokmanović L, Janković S, Suvajdžić-Vuković N, Tomin D, Perisić O, Rakocević G, Popović M, Pavlović S, Tošić N. Parallel targeted next generation sequencing of childhood and adult acute myeloid leukemia patients reveals uniform genomic profile of the disease. in Tumor Biology. 2016;37(10):13391-13401.
doi:10.1007/s13277-016-5142-7 .

Marjanović, Irena, Perić, Jelena, Stanić, Bojana, Pejanović, Nadja, Lucić, Bojana, Karan-Đurašević, Teodora, Janić, Dragana, Dokmanović, Lidija, Janković, Srdja, Suvajdžić-Vuković, Nada, Tomin, Dragica, Perisić, Ognjen, Rakocević, Goran, Popović, Milos, Pavlović, Sonja, Tošić, Nataša, "Parallel targeted next generation sequencing of childhood and adult acute myeloid leukemia patients reveals uniform genomic profile of the disease" in Tumor Biology, 37, no. 10 (2016):13391-13401,
https://doi.org/10.1007/s13277-016-5142-7 . .