Kostić, Tatjana

Link to this page

Authority KeyName Variants
orcid::0000-0001-9350-9102
  • Kostić, Tatjana (25)
  • Kostić, Tatjana (12)
Projects

Author's Bibliography

Expression Pattern and Prognostic Significance of the Long Non-Coding RNA Metastasis-Associated Lung Adenocarcinoma Transcript 1 in Chronic Lymphocytic Leukemia

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

(MDPI, 2024)

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 . .

Expression Pattern and Prognostic Significance of the Long Non-Coding RNA Metastasis-Associated Lung Adenocarcinoma Transcript 1 in Chronic Lymphocytic Leukemia

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

(MDPI, 2024)

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 . .

Prognostic significance of the long non-coding rna malat1 expression in chronic lymphocytic leukemia

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

(Institute of Molecular Genetics and Genetic Engineering (IMGGE), University of Belgrade, 2023)

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 .

Detection of preleukemic clones in neonatal blood spots of children with B-cell precursor acute lymphoblastic leukemia

Karan-Đurašević, Teodora; Kaćanski, Nataša; Kostić, Tatjana; Marjanović, Irena; Tošić, Nataša; Perić, Jelena; Kolarović, Jovanka; Janić, Dragana; Pavlović, Sonja

(Institute of Molecular Genetics and Genetic Engineering (IMGGE), University of Belgrade, 2023)

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 .

PB1917: EXPRESSION OF THE LONG NON-CODING RNA MALAT1 IN CHRONIC LYMPHOCYTIC LEUKEMIA

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

(2023)

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 . .

Presence of leukemic clone-specific immunoglobulin heavy chain rearrangements in neonatal blood spots of children with B-cell precursor acute lymphoblastic leukemia

Kačanski, Nataša; Kolarović, Jovanka; Kostić, Tatjana; Marjanović, Irena; Janić, Dragana; Pavlović, Sonja; Karan-Đurašević, Teodora

(John Wiley & Sons Ltd, 2023)

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 . .

Expression of BCL11A in chronic lymphocytic leukaemia

Tošić, Nataša; Ugrin, Milena; Marjanović, Irena; Kostić, Tatjana; Vuković, Vojin; Tomić, Kristina; Otasević, Vladimir; Antić, Darko; Mihaljević, Biljana; Pavlović, Sonja; Karan-Đurašević, Teodora

(Wiley, Hoboken, 2023)

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 . .
2
3
2

Uporedna analiza internacionalnog prognostičkog indeksa za hroničnu limfocitnu leukemiju, skora rizika od progresije i skora Centra za rak MD Anderson - iskustvo jednog centra

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

(Srpsko lekarsko društvo, Beograd, 2021)

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 . .

Prognostic significance of combined BAALC and MN1 gene expression level in acute myeloid leukemia with normal karyotype

Marjanović, Irena; Karan-Đurašević, Teodora; Kostić, Tatjana; Virijević, Marijana; Suvajdžić-Vuković, Nada; Pavlović, Sonja; Tošić, Nataša

(Wiley, Hoboken, 2021)

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 . .
1
2
2

Association of SLC28A3 Gene Expression and CYP2B6*6 Allele with the Response to Fludarabine Plus Cyclophosphamide in Chronic Lymphocytic Leukemia Patients

Vuković, Vojin; Karan-Đurašević, Teodora; Antić, Darko; Tošić, Nataša; Kostić, Tatjana; Marjanović, Irena; Denčić-Fekete, Marija; Đurašinović, Vladislava; Pavlović, Sonja; Mihaljević, Biljana

(Frontiers Media Sa, Lausanne, 2020)

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 . .
2
1
2

Expression Pattern and Prognostic Significance of EVI1 Gene in Adult Acute Myeloid Leukemia Patients with Normal Karyotype

Marjanović, Irena; Karan-Đurašević, Teodora; Kostić, Tatjana; Virijević, Marijana; Suvajdžić-Vuković, Nada; Pavlović, Sonja; Tošić, Nataša

(Springer India, New Delhi, 2020)

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 . .
1
7
4
6

Akutna promijelocitna leukemija bez t(15;17) - molekularni dokazi atipične PML/RAR-α transkripcione varijante genskim sekvenciranjem

Đorđević, Vesna; Tošić, Nataša; Denčić-Fekete, Marija; Virijević, Marijana; Jovanović, Jelica; Jaković, Ljubomir; Kraguljac-Kurtović, Nada; Bogdanović, Andrija; Kostić, Tatjana; Pavlović, Sonja

(Vojnomedicinska akademija - Institut za naučne informacije, Beograd, 2020)

TY  - JOUR
AU  - Đorđević, Vesna
AU  - Tošić, Nataša
AU  - Denčić-Fekete, Marija
AU  - Virijević, Marijana
AU  - Jovanović, Jelica
AU  - Jaković, Ljubomir
AU  - Kraguljac-Kurtović, Nada
AU  - Bogdanović, Andrija
AU  - Kostić, Tatjana
AU  - Pavlović, Sonja
PY  - 2020
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/1371
AB  - Uvod. Precizno dijagnostikovanje akutne promijelocitne leukemije (APL), ne samo na osnovu morfoloških i kliničkih parametara, već i na molekularnom nivou, veoma je važno radi primene adekvatne ciljane terapije. Prikaz bolesnika. Prikazali smo bolesnicu, staru 62 godine, sa dijagnozom APL. Primenom standardne citogenetičke analize, kao i primenom fluorescentne in situ hibridizacije (FISH), nije bilo potvrđeno prisustvo t(15;17) kod opisane bolesnice. Primenom metode reverzna transkriptazalančana reakcija polimeraze (RT-PCR), identifikovana su dva atipična promyelotic leukemia/retinoic acid receptor alpha (PML/RAR-α) fuziona transkripta. Oba transkripta su predstavljala izoforme. Duži transkript je zadržao "okvir čitanja" i kodirao je funkcionalan PML/RAR-α aberantni protein, dok je kraći transkript bio van "okvira čitanja". Zaključak. Naša studija ukazuje na potrebu za primenom molekularne metodologije u svakodnevnoj kliničkoj praksi. Precizna karakterizacija PML/RAR-α fuzionih transkipta čini osnovu za identifikovanje retkih bolesnika čije lečenje zahteva dodatni oprez. Prema našim saznanjima, ovo je tek peti slučaj opisanog atipičnog PML/RAR-α transkripta koji u sebi sadrži celokupan PML egzon 7a, a među njima jedini koji se nije mogao detektovati primenom citogenetičke i FISH analize. Svi ovde predstavljeni slučajevi su imali smrtni ishod. Zbog toga, naši rezulatati, zajedno sa sličnim slučajevima opisanim u literaturi, naglašavaju značaj detaljne identifikacije atipičnih PML/RAR-α fuzija, ne samo u svrhu prepoznavanja njihove uloge u procesu leukemogeneze, veći i u smislu procene njihovog uticaja na ishod lečenja.
AB  - Introduction. The accurate diagnosis of acute promyelocytic leukemia (APL), not only on the morphological and clinical, but also on the molecular level, is very important for application of targeted therapies. Case report. A 62year-old woman presented with APL. By using conventional cytogenetic analysis as well as applying the fluorescence in situ hybridization (FISH) analysis it has not been possible to confirm the presence of t(15;17) in the presented patient. Using reverse transcriptase polymerase chain reaction (RT-PCR) two atypical promyelotic leukemia/retinoic acid receptor alpha (PML/RAR-α) fusion transcripts were identified. Both detected transcripts were isoforms. The larger transcript was in-frame, coding for functional aberrant PML/RAR-α protein, while the shorter transcript was an out-of-frame. Conclusion. Our study highlights the need for the application of molecular methodology in daily clinical practice. Precise characterization of PML/RAR-α fusion transcript creates a basis for identifying rare individual cases that require special caution when treating such patients. To our knowledge this is only the fifth case of atypical PML/RAR-α transcript containing full PML exon 7a, and among them the only one that was cytogenetically cryptic and FISH negative. All of the herein presented cases had lethal outcome. Therefore, our findings with the additional review of the literature, emphasizes the importance of detailed identification of atypical PML/RAR-α fusions, not only for the purpose of knowing their role in leukemogenesis, but also for the assessment of the impact that they can have on the outcome of the treatment.
PB  - Vojnomedicinska akademija - Institut za naučne informacije, Beograd
T2  - Vojnosanitetski pregled
T1  - Akutna promijelocitna leukemija bez t(15;17) - molekularni dokazi atipične PML/RAR-α transkripcione varijante genskim sekvenciranjem
T1  - Acute promyelocytic leukemia lacking t(15;17): Molecular evidence of atypical PML/RAR-α transcriptional variant by gene sequencing
EP  - 102
IS  - 1
SP  - 97
VL  - 77
DO  - 10.2298/VSP170620040D
ER  - 
@article{
author = "Đorđević, Vesna and Tošić, Nataša and Denčić-Fekete, Marija and Virijević, Marijana and Jovanović, Jelica and Jaković, Ljubomir and Kraguljac-Kurtović, Nada and Bogdanović, Andrija and Kostić, Tatjana and Pavlović, Sonja",
year = "2020",
abstract = "Uvod. Precizno dijagnostikovanje akutne promijelocitne leukemije (APL), ne samo na osnovu morfoloških i kliničkih parametara, već i na molekularnom nivou, veoma je važno radi primene adekvatne ciljane terapije. Prikaz bolesnika. Prikazali smo bolesnicu, staru 62 godine, sa dijagnozom APL. Primenom standardne citogenetičke analize, kao i primenom fluorescentne in situ hibridizacije (FISH), nije bilo potvrđeno prisustvo t(15;17) kod opisane bolesnice. Primenom metode reverzna transkriptazalančana reakcija polimeraze (RT-PCR), identifikovana su dva atipična promyelotic leukemia/retinoic acid receptor alpha (PML/RAR-α) fuziona transkripta. Oba transkripta su predstavljala izoforme. Duži transkript je zadržao "okvir čitanja" i kodirao je funkcionalan PML/RAR-α aberantni protein, dok je kraći transkript bio van "okvira čitanja". Zaključak. Naša studija ukazuje na potrebu za primenom molekularne metodologije u svakodnevnoj kliničkoj praksi. Precizna karakterizacija PML/RAR-α fuzionih transkipta čini osnovu za identifikovanje retkih bolesnika čije lečenje zahteva dodatni oprez. Prema našim saznanjima, ovo je tek peti slučaj opisanog atipičnog PML/RAR-α transkripta koji u sebi sadrži celokupan PML egzon 7a, a među njima jedini koji se nije mogao detektovati primenom citogenetičke i FISH analize. Svi ovde predstavljeni slučajevi su imali smrtni ishod. Zbog toga, naši rezulatati, zajedno sa sličnim slučajevima opisanim u literaturi, naglašavaju značaj detaljne identifikacije atipičnih PML/RAR-α fuzija, ne samo u svrhu prepoznavanja njihove uloge u procesu leukemogeneze, veći i u smislu procene njihovog uticaja na ishod lečenja., Introduction. The accurate diagnosis of acute promyelocytic leukemia (APL), not only on the morphological and clinical, but also on the molecular level, is very important for application of targeted therapies. Case report. A 62year-old woman presented with APL. By using conventional cytogenetic analysis as well as applying the fluorescence in situ hybridization (FISH) analysis it has not been possible to confirm the presence of t(15;17) in the presented patient. Using reverse transcriptase polymerase chain reaction (RT-PCR) two atypical promyelotic leukemia/retinoic acid receptor alpha (PML/RAR-α) fusion transcripts were identified. Both detected transcripts were isoforms. The larger transcript was in-frame, coding for functional aberrant PML/RAR-α protein, while the shorter transcript was an out-of-frame. Conclusion. Our study highlights the need for the application of molecular methodology in daily clinical practice. Precise characterization of PML/RAR-α fusion transcript creates a basis for identifying rare individual cases that require special caution when treating such patients. To our knowledge this is only the fifth case of atypical PML/RAR-α transcript containing full PML exon 7a, and among them the only one that was cytogenetically cryptic and FISH negative. All of the herein presented cases had lethal outcome. Therefore, our findings with the additional review of the literature, emphasizes the importance of detailed identification of atypical PML/RAR-α fusions, not only for the purpose of knowing their role in leukemogenesis, but also for the assessment of the impact that they can have on the outcome of the treatment.",
publisher = "Vojnomedicinska akademija - Institut za naučne informacije, Beograd",
journal = "Vojnosanitetski pregled",
title = "Akutna promijelocitna leukemija bez t(15;17) - molekularni dokazi atipične PML/RAR-α transkripcione varijante genskim sekvenciranjem, Acute promyelocytic leukemia lacking t(15;17): Molecular evidence of atypical PML/RAR-α transcriptional variant by gene sequencing",
pages = "102-97",
number = "1",
volume = "77",
doi = "10.2298/VSP170620040D"
}
Đorđević, V., Tošić, N., Denčić-Fekete, M., Virijević, M., Jovanović, J., Jaković, L., Kraguljac-Kurtović, N., Bogdanović, A., Kostić, T.,& Pavlović, S.. (2020). Akutna promijelocitna leukemija bez t(15;17) - molekularni dokazi atipične PML/RAR-α transkripcione varijante genskim sekvenciranjem. in Vojnosanitetski pregled
Vojnomedicinska akademija - Institut za naučne informacije, Beograd., 77(1), 97-102.
https://doi.org/10.2298/VSP170620040D
Đorđević V, Tošić N, Denčić-Fekete M, Virijević M, Jovanović J, Jaković L, Kraguljac-Kurtović N, Bogdanović A, Kostić T, Pavlović S. Akutna promijelocitna leukemija bez t(15;17) - molekularni dokazi atipične PML/RAR-α transkripcione varijante genskim sekvenciranjem. in Vojnosanitetski pregled. 2020;77(1):97-102.
doi:10.2298/VSP170620040D .
Đorđević, Vesna, Tošić, Nataša, Denčić-Fekete, Marija, Virijević, Marijana, Jovanović, Jelica, Jaković, Ljubomir, Kraguljac-Kurtović, Nada, Bogdanović, Andrija, Kostić, Tatjana, Pavlović, Sonja, "Akutna promijelocitna leukemija bez t(15;17) - molekularni dokazi atipične PML/RAR-α transkripcione varijante genskim sekvenciranjem" in Vojnosanitetski pregled, 77, no. 1 (2020):97-102,
https://doi.org/10.2298/VSP170620040D . .
1
1
1

Primena ciljanog sekvenciranja nove generacije u analizi mutacionog profila pacijenata sa akutnom limfoblastnom leukemijom

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

(Društvo medicinskih biohemičara Srbije, Beograd i Versita, 2020)

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 . .
2
1

The influence of Wilms' tumor 1 gene expression level on prognosis and risk stratification of acute promyelocytic leukemia patients

Mitrović, Mirjana; Kostić, Tatjana; Virijević, Marijana; Karan-Đurašević, Teodora; Suvajdžić-Vuković, Nada; Pavlović, Sonja; Tošić, Nataša

(Wiley, Hoboken, 2020)

TY  - JOUR
AU  - Mitrović, Mirjana
AU  - Kostić, Tatjana
AU  - Virijević, Marijana
AU  - Karan-Đurašević, Teodora
AU  - Suvajdžić-Vuković, Nada
AU  - Pavlović, Sonja
AU  - Tošić, Nataša
PY  - 2020
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/1403
AB  - Introduction Patients with acute promyelocytic leukemia (APL) are characterized by the highest expression of Wilms' tumor 1 (WT1) gene compared with other subtypes of acute myeloid leukemia, and yet this molecular marker is almost never used for risk stratification and in therapy response monitoring. Methods Quantitative assessment of Wilms' tumor 1 (WT1) gene transcripts was performed using real-time PCR method. The bone marrow samples were collected at the time of diagnosis for 47 APL patients, and for 31/47 patients during follow-up/relapse of the disease (129 samples in total). We examined how this molecular marker can be used for prognosis and minimal residual disease (MRD) monitoring. Results Increased WT1 expression was found in 34% of patients. WT1(high) status was an independent unfavorable factor for early death occurrence and was associated with shorter overall survival (OS). Assessment of log reduction value of WT1 expression in paired diagnosis/complete remission samples did not reveal its impact on relapse rate, disease-free survival, and OS. Also, measurement of WT1 expression level at different time points during therapy was not a reliable method for MRD monitoring. Conclusion Increased expression of WT1 gene detected in high proportion of APL patients could be considered as a marker for more precise risk stratification models in an attempt to further improve treatment and outcome of APL patients.
PB  - Wiley, Hoboken
T2  - International Journal of Laboratory Hematology
T1  - The influence of Wilms' tumor 1 gene expression level on prognosis and risk stratification of acute promyelocytic leukemia patients
EP  - 87
IS  - 1
SP  - 82
VL  - 42
DO  - 10.1111/ijlh.13144
ER  - 
@article{
author = "Mitrović, Mirjana and Kostić, Tatjana and Virijević, Marijana and Karan-Đurašević, Teodora and Suvajdžić-Vuković, Nada and Pavlović, Sonja and Tošić, Nataša",
year = "2020",
abstract = "Introduction Patients with acute promyelocytic leukemia (APL) are characterized by the highest expression of Wilms' tumor 1 (WT1) gene compared with other subtypes of acute myeloid leukemia, and yet this molecular marker is almost never used for risk stratification and in therapy response monitoring. Methods Quantitative assessment of Wilms' tumor 1 (WT1) gene transcripts was performed using real-time PCR method. The bone marrow samples were collected at the time of diagnosis for 47 APL patients, and for 31/47 patients during follow-up/relapse of the disease (129 samples in total). We examined how this molecular marker can be used for prognosis and minimal residual disease (MRD) monitoring. Results Increased WT1 expression was found in 34% of patients. WT1(high) status was an independent unfavorable factor for early death occurrence and was associated with shorter overall survival (OS). Assessment of log reduction value of WT1 expression in paired diagnosis/complete remission samples did not reveal its impact on relapse rate, disease-free survival, and OS. Also, measurement of WT1 expression level at different time points during therapy was not a reliable method for MRD monitoring. Conclusion Increased expression of WT1 gene detected in high proportion of APL patients could be considered as a marker for more precise risk stratification models in an attempt to further improve treatment and outcome of APL patients.",
publisher = "Wiley, Hoboken",
journal = "International Journal of Laboratory Hematology",
title = "The influence of Wilms' tumor 1 gene expression level on prognosis and risk stratification of acute promyelocytic leukemia patients",
pages = "87-82",
number = "1",
volume = "42",
doi = "10.1111/ijlh.13144"
}
Mitrović, M., Kostić, T., Virijević, M., Karan-Đurašević, T., Suvajdžić-Vuković, N., Pavlović, S.,& Tošić, N.. (2020). The influence of Wilms' tumor 1 gene expression level on prognosis and risk stratification of acute promyelocytic leukemia patients. in International Journal of Laboratory Hematology
Wiley, Hoboken., 42(1), 82-87.
https://doi.org/10.1111/ijlh.13144
Mitrović M, Kostić T, Virijević M, Karan-Đurašević T, Suvajdžić-Vuković N, Pavlović S, Tošić N. The influence of Wilms' tumor 1 gene expression level on prognosis and risk stratification of acute promyelocytic leukemia patients. in International Journal of Laboratory Hematology. 2020;42(1):82-87.
doi:10.1111/ijlh.13144 .
Mitrović, Mirjana, Kostić, Tatjana, Virijević, Marijana, Karan-Đurašević, Teodora, Suvajdžić-Vuković, Nada, Pavlović, Sonja, Tošić, Nataša, "The influence of Wilms' tumor 1 gene expression level on prognosis and risk stratification of acute promyelocytic leukemia patients" in International Journal of Laboratory Hematology, 42, no. 1 (2020):82-87,
https://doi.org/10.1111/ijlh.13144 . .
1
9
2
7

Rearanžmani gena za teški lanac imunoglobulina u bolesnika sa Gošeovom bolešću

Rodić, Predrag; Lakočević, Milan; Pavlović, Sonja; Karan-Đurašević, Teodora; Kostić, Tatjana; Suvajdžić-Vuković, Nada; Šumarac, Zorica; Petakov, Milan; Janić, Dragana

(Društvo medicinskih biohemičara Srbije, Beograd i Versita, 2018)

TY  - JOUR
AU  - Rodić, Predrag
AU  - Lakočević, Milan
AU  - Pavlović, Sonja
AU  - Karan-Đurašević, Teodora
AU  - Kostić, Tatjana
AU  - Suvajdžić-Vuković, Nada
AU  - Šumarac, Zorica
AU  - Petakov, Milan
AU  - Janić, Dragana
PY  - 2018
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/1113
AB  - Uvod: Nekoliko studija u literaturi navode dokaze o povećanoj incidenci hematoloških komplikacija u bolesnika sa Gošeovom bolešću, uključujući monoklonsku i poliklonsku gamapatiju i hematološke malignitete, a posebno multipli mijelom. Metode: Određivana je serumska koncentracija imunoglobulina kao i rearanžman gena za teški lanac imunoglobulina - IGH, PCR analizom. Klonalni PCR produkti su direktno sekvencirani i analizirani koristeći adekvatne alate i baze podataka. Monoklonski proteini seruma su detektovani i identifikovani metodom elektroforeze. Rezultati: Među 27 bolesnika, klonalni IGH rearanžman je otkriven kod osmoro, od kojih je petoro imalo i monot klonski protein u serumu. Hipergamaglobulinemija je otkrivena u 9/27 bolesnika. Podaci o praćenju za 17 bolesnika su pokazali da je klonalni rearanžman ostao isti u četiri bolesnika, dok je u jednog bolesnika iščezao tokom perioda praćenja. Preostalih 12/17 bolesnika nisu imali klonalni IGH rearanžman niti su ga stekli nakon perioda praćenja. Zaključak: Iako klonska ekspanzija može da nastane relativno rano u toku Gošeove bolesti, barem sudeći prema rearanžmanu IGH gena, detektovani klonovi mogu biti tranzitorni. Pažljivo kliničko praćenje ovih bolesnika je obavezno, uključujući i nadzor nad limfoidnim neoplazmama, posebno multiplim mijelomom.
AB  - Background: Several studies support the evidence of increased incidence of hematological complications in Gaucher disease including monoclonal and polyclonal gammopathies and blood malignancies, especially multiple myeloma. Methods: Serum concentrations of immunoglobulins and PCR analysis of the IGH gene rearrangements were performed. The clonal PCR products were directly sequenced and analyzed with the appropriate database and tools. Serum monoclonal proteins were detected and identified by electrophoresis. Results: Among 27 Gaucher patients, clonal IGH rearrangement was discovered in eight, with 5/8 having also serum monoclonal protein. Elevated immunoglobulins were detected in 9/27 patients. Follow-up data for 17 patients showed that the clonal rearrangement remained the same in four of them, however, in one patient it disappeared after the follow-up period. The remaining 12/17 patients were without previous IGH clonal rearrangement and remained so after the follow-up. Conclusions: Although clonal expansion may occur relatively early in the disease course, at least judging by the IGH gene rearrangements in Gaucher patients, the detected clones may be transient. A careful clinical follow-up in these patients is mandatory, including monitoring for lymphoid neoplasms, especially multiple myeloma.
PB  - Društvo medicinskih biohemičara Srbije, Beograd i Versita
T2  - Journal of Medical Biochemistry
T1  - Rearanžmani gena za teški lanac imunoglobulina u bolesnika sa Gošeovom bolešću
T1  - Immunoglobulin heavy chain gene rearrangements in patients with Gaucher disease
EP  - 312
IS  - 3
SP  - 307
VL  - 37
DO  - 10.1515/jomb-2017-0061
ER  - 
@article{
author = "Rodić, Predrag and Lakočević, Milan and Pavlović, Sonja and Karan-Đurašević, Teodora and Kostić, Tatjana and Suvajdžić-Vuković, Nada and Šumarac, Zorica and Petakov, Milan and Janić, Dragana",
year = "2018",
abstract = "Uvod: Nekoliko studija u literaturi navode dokaze o povećanoj incidenci hematoloških komplikacija u bolesnika sa Gošeovom bolešću, uključujući monoklonsku i poliklonsku gamapatiju i hematološke malignitete, a posebno multipli mijelom. Metode: Određivana je serumska koncentracija imunoglobulina kao i rearanžman gena za teški lanac imunoglobulina - IGH, PCR analizom. Klonalni PCR produkti su direktno sekvencirani i analizirani koristeći adekvatne alate i baze podataka. Monoklonski proteini seruma su detektovani i identifikovani metodom elektroforeze. Rezultati: Među 27 bolesnika, klonalni IGH rearanžman je otkriven kod osmoro, od kojih je petoro imalo i monot klonski protein u serumu. Hipergamaglobulinemija je otkrivena u 9/27 bolesnika. Podaci o praćenju za 17 bolesnika su pokazali da je klonalni rearanžman ostao isti u četiri bolesnika, dok je u jednog bolesnika iščezao tokom perioda praćenja. Preostalih 12/17 bolesnika nisu imali klonalni IGH rearanžman niti su ga stekli nakon perioda praćenja. Zaključak: Iako klonska ekspanzija može da nastane relativno rano u toku Gošeove bolesti, barem sudeći prema rearanžmanu IGH gena, detektovani klonovi mogu biti tranzitorni. Pažljivo kliničko praćenje ovih bolesnika je obavezno, uključujući i nadzor nad limfoidnim neoplazmama, posebno multiplim mijelomom., Background: Several studies support the evidence of increased incidence of hematological complications in Gaucher disease including monoclonal and polyclonal gammopathies and blood malignancies, especially multiple myeloma. Methods: Serum concentrations of immunoglobulins and PCR analysis of the IGH gene rearrangements were performed. The clonal PCR products were directly sequenced and analyzed with the appropriate database and tools. Serum monoclonal proteins were detected and identified by electrophoresis. Results: Among 27 Gaucher patients, clonal IGH rearrangement was discovered in eight, with 5/8 having also serum monoclonal protein. Elevated immunoglobulins were detected in 9/27 patients. Follow-up data for 17 patients showed that the clonal rearrangement remained the same in four of them, however, in one patient it disappeared after the follow-up period. The remaining 12/17 patients were without previous IGH clonal rearrangement and remained so after the follow-up. Conclusions: Although clonal expansion may occur relatively early in the disease course, at least judging by the IGH gene rearrangements in Gaucher patients, the detected clones may be transient. A careful clinical follow-up in these patients is mandatory, including monitoring for lymphoid neoplasms, especially multiple myeloma.",
publisher = "Društvo medicinskih biohemičara Srbije, Beograd i Versita",
journal = "Journal of Medical Biochemistry",
title = "Rearanžmani gena za teški lanac imunoglobulina u bolesnika sa Gošeovom bolešću, Immunoglobulin heavy chain gene rearrangements in patients with Gaucher disease",
pages = "312-307",
number = "3",
volume = "37",
doi = "10.1515/jomb-2017-0061"
}
Rodić, P., Lakočević, M., Pavlović, S., Karan-Đurašević, T., Kostić, T., Suvajdžić-Vuković, N., Šumarac, Z., Petakov, M.,& Janić, D.. (2018). Rearanžmani gena za teški lanac imunoglobulina u bolesnika sa Gošeovom bolešću. in Journal of Medical Biochemistry
Društvo medicinskih biohemičara Srbije, Beograd i Versita., 37(3), 307-312.
https://doi.org/10.1515/jomb-2017-0061
Rodić P, Lakočević M, Pavlović S, Karan-Đurašević T, Kostić T, Suvajdžić-Vuković N, Šumarac Z, Petakov M, Janić D. Rearanžmani gena za teški lanac imunoglobulina u bolesnika sa Gošeovom bolešću. in Journal of Medical Biochemistry. 2018;37(3):307-312.
doi:10.1515/jomb-2017-0061 .
Rodić, Predrag, Lakočević, Milan, Pavlović, Sonja, Karan-Đurašević, Teodora, Kostić, Tatjana, Suvajdžić-Vuković, Nada, Šumarac, Zorica, Petakov, Milan, Janić, Dragana, "Rearanžmani gena za teški lanac imunoglobulina u bolesnika sa Gošeovom bolešću" in Journal of Medical Biochemistry, 37, no. 3 (2018):307-312,
https://doi.org/10.1515/jomb-2017-0061 . .
3
3

Targeted mutational profiling of childhood and adult acute lymphoblastic leukemia patients

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

(Ferrata Storti Foundation, Pavia, 2017)

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 .

Udruženost ekspresije Bax gena i Bcl2/Bax odnosa sa kliničkim i molekularnim prognostičkim markerima u hroničnoj limfocitnoj leukemiji

Vučićević, Ksenija; Jakovljević, Vladimir; Čolović, Nataša; Tošić, Nataša; Kostić, Tatjana; Glumac, Irena; Pavlović, Sonja; Karan-Đurašević, Teodora; Čolović, Milica

(Društvo medicinskih biohemičara Srbije, Beograd i Versita, 2016)

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 . .
52
8
46

Assessment of BAALC and MN1 gene expression level could contribute to improved prognostic stratification of the aml-nk patients

Marjanović, Irena; Karan-Đurašević, Teodora; Kostić, Jelena; Kostić, Tatjana ; Virijević, M.; Djunić, I.; Suvajdžić-Vuković, Nada; Tomin, D.; Pavlović, Sonja; Tošić, Nataša

(Ferrata Storti Foundation, Pavia, 2016)

TY  - CONF
AU  - Marjanović, Irena
AU  - Karan-Đurašević, Teodora
AU  - Kostić, Jelena
AU  - Kostić, Tatjana 
AU  - Virijević, M.
AU  - Djunić, I.
AU  - Suvajdžić-Vuković, Nada
AU  - Tomin, D.
AU  - Pavlović, Sonja
AU  - Tošić, Nataša
PY  - 2016
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/911
PB  - Ferrata Storti Foundation, Pavia
C3  - Haematologica-The Hematology Journal
T1  - Assessment of BAALC and MN1 gene expression level could contribute to improved prognostic stratification of the aml-nk patients
EP  - 382
SP  - 382
VL  - 101
UR  - https://hdl.handle.net/21.15107/rcub_imagine_911
ER  - 
@conference{
author = "Marjanović, Irena and Karan-Đurašević, Teodora and Kostić, Jelena and Kostić, Tatjana  and Virijević, M. and Djunić, I. and Suvajdžić-Vuković, Nada and Tomin, D. and Pavlović, Sonja and Tošić, Nataša",
year = "2016",
publisher = "Ferrata Storti Foundation, Pavia",
journal = "Haematologica-The Hematology Journal",
title = "Assessment of BAALC and MN1 gene expression level could contribute to improved prognostic stratification of the aml-nk patients",
pages = "382-382",
volume = "101",
url = "https://hdl.handle.net/21.15107/rcub_imagine_911"
}
Marjanović, I., Karan-Đurašević, T., Kostić, J., Kostić, T., Virijević, M., Djunić, I., Suvajdžić-Vuković, N., Tomin, D., Pavlović, S.,& Tošić, N.. (2016). Assessment of BAALC and MN1 gene expression level could contribute to improved prognostic stratification of the aml-nk patients. in Haematologica-The Hematology Journal
Ferrata Storti Foundation, Pavia., 101, 382-382.
https://hdl.handle.net/21.15107/rcub_imagine_911
Marjanović I, Karan-Đurašević T, Kostić J, Kostić T, Virijević M, Djunić I, Suvajdžić-Vuković N, Tomin D, Pavlović S, Tošić N. Assessment of BAALC and MN1 gene expression level could contribute to improved prognostic stratification of the aml-nk patients. in Haematologica-The Hematology Journal. 2016;101:382-382.
https://hdl.handle.net/21.15107/rcub_imagine_911 .
Marjanović, Irena, Karan-Đurašević, Teodora, Kostić, Jelena, Kostić, Tatjana , Virijević, M., Djunić, I., Suvajdžić-Vuković, Nada, Tomin, D., Pavlović, Sonja, Tošić, Nataša, "Assessment of BAALC and MN1 gene expression level could contribute to improved prognostic stratification of the aml-nk patients" in Haematologica-The Hematology Journal, 101 (2016):382-382,
https://hdl.handle.net/21.15107/rcub_imagine_911 .

JAK2V617F mutacija kod bolesnika sa B ćelijskom hroničnom limfocitnom leukemijom i prefibrotičkom primarnom mijelofibrozom

Ristić, Slobodan; Radojković, Milica; Kostić, Tatjana; Spasovski, Vesna; Pavlović, Sonja; Čemerikić-Martinović, Vesna

(Srpsko lekarsko društvo, Beograd, 2015)

TY  - JOUR
AU  - Ristić, Slobodan
AU  - Radojković, Milica
AU  - Kostić, Tatjana
AU  - Spasovski, Vesna
AU  - Pavlović, Sonja
AU  - Čemerikić-Martinović, Vesna
PY  - 2015
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/800
AB  - Uvod Sekundarni maligniteti, naročito solidni tumori, česti su kod bolesnika s hroničnom limfocitnom leukemijom (HLL), ali retko se sreće udruženost mijeloproliferativnih neoplazmi i HLL. Prikaz bolesnika Prikazujemo muškarca starog 67 godina sa B ćelijskom HLL kod koga se nakon devet godina razvila primarna mijelofibroza (PMF). Bolesnik je lečen alkilišućim agensima i analozima purina, što može biti predisponirajući faktor za razvoj mijeloproliferativnog oboljenja. JAK2V617F mutacija nije otkrivena prilikom postavljanja dijagnoze HLL, ali je utvrđena posle devet godina, kada se razvila PMF, što ukazuje na to da su B ćelijska HLL i PMF neoplazme koje potiču od različitih ćelijskih klonova. Zaključak Patogenetski mehanizmi udruženosti mijeloproliferativne i limfoproliferativne neoplazme kod bolesnika nisu razjašnjeni. Potrebna su dalja istraživanja radi utvrđivanja da li ove maligne bolesti potiču od dva različita ćelijska klona ili nastaju od iste pluripotentne matične ćelije hematopoeze.
AB  - Introduction Secondary malignancies, particularly solid tumors, are common in patients with chronic lymphocytic leukemia (CLL), but association of myeloproliferative neoplasms and chronic lymphocytic leukemia in the same patient is very rare. Case Outline We report of a 67-year-old man with B-cell chronic lymphoid leukemia (B-CLL) who developed primary myelofibrosis (PMF) nine years after initial diagnosis. Patient received alkylation agents and purine analogue, which can be a predisposing factor for the development of myeloproliferative neoplasms. JAK2V617F mutation was not present initially at the time of CLL diagnosis, but was found after nine years when PMF occurred, which indicates that B-CLL and PMF represent two separate clonal origin neoplasms. Conclusion Pathogenic mechanisms for the development of myeloproliferative and lymphoproliferative neoplasms in the same patient are unknown. Further research is needed to determine whether these malignancies originate from two different cell clones or arise from the same pluripotent hematopoietic stem cell.
PB  - Srpsko lekarsko društvo, Beograd
T2  - Srpski arhiv za celokupno lekarstvo
T1  - JAK2V617F mutacija kod bolesnika sa B ćelijskom hroničnom limfocitnom leukemijom i prefibrotičkom primarnom mijelofibrozom
T1  - JAK2V617F mutation in a patient with B-cell chronic lymphocytic leukemia and prefibrotic primary myelofibrosis
EP  - 743
IS  - 11-12
SP  - 739
VL  - 143
DO  - 10.2298/SARH1512739R
ER  - 
@article{
author = "Ristić, Slobodan and Radojković, Milica and Kostić, Tatjana and Spasovski, Vesna and Pavlović, Sonja and Čemerikić-Martinović, Vesna",
year = "2015",
abstract = "Uvod Sekundarni maligniteti, naročito solidni tumori, česti su kod bolesnika s hroničnom limfocitnom leukemijom (HLL), ali retko se sreće udruženost mijeloproliferativnih neoplazmi i HLL. Prikaz bolesnika Prikazujemo muškarca starog 67 godina sa B ćelijskom HLL kod koga se nakon devet godina razvila primarna mijelofibroza (PMF). Bolesnik je lečen alkilišućim agensima i analozima purina, što može biti predisponirajući faktor za razvoj mijeloproliferativnog oboljenja. JAK2V617F mutacija nije otkrivena prilikom postavljanja dijagnoze HLL, ali je utvrđena posle devet godina, kada se razvila PMF, što ukazuje na to da su B ćelijska HLL i PMF neoplazme koje potiču od različitih ćelijskih klonova. Zaključak Patogenetski mehanizmi udruženosti mijeloproliferativne i limfoproliferativne neoplazme kod bolesnika nisu razjašnjeni. Potrebna su dalja istraživanja radi utvrđivanja da li ove maligne bolesti potiču od dva različita ćelijska klona ili nastaju od iste pluripotentne matične ćelije hematopoeze., Introduction Secondary malignancies, particularly solid tumors, are common in patients with chronic lymphocytic leukemia (CLL), but association of myeloproliferative neoplasms and chronic lymphocytic leukemia in the same patient is very rare. Case Outline We report of a 67-year-old man with B-cell chronic lymphoid leukemia (B-CLL) who developed primary myelofibrosis (PMF) nine years after initial diagnosis. Patient received alkylation agents and purine analogue, which can be a predisposing factor for the development of myeloproliferative neoplasms. JAK2V617F mutation was not present initially at the time of CLL diagnosis, but was found after nine years when PMF occurred, which indicates that B-CLL and PMF represent two separate clonal origin neoplasms. Conclusion Pathogenic mechanisms for the development of myeloproliferative and lymphoproliferative neoplasms in the same patient are unknown. Further research is needed to determine whether these malignancies originate from two different cell clones or arise from the same pluripotent hematopoietic stem cell.",
publisher = "Srpsko lekarsko društvo, Beograd",
journal = "Srpski arhiv za celokupno lekarstvo",
title = "JAK2V617F mutacija kod bolesnika sa B ćelijskom hroničnom limfocitnom leukemijom i prefibrotičkom primarnom mijelofibrozom, JAK2V617F mutation in a patient with B-cell chronic lymphocytic leukemia and prefibrotic primary myelofibrosis",
pages = "743-739",
number = "11-12",
volume = "143",
doi = "10.2298/SARH1512739R"
}
Ristić, S., Radojković, M., Kostić, T., Spasovski, V., Pavlović, S.,& Čemerikić-Martinović, V.. (2015). JAK2V617F mutacija kod bolesnika sa B ćelijskom hroničnom limfocitnom leukemijom i prefibrotičkom primarnom mijelofibrozom. in Srpski arhiv za celokupno lekarstvo
Srpsko lekarsko društvo, Beograd., 143(11-12), 739-743.
https://doi.org/10.2298/SARH1512739R
Ristić S, Radojković M, Kostić T, Spasovski V, Pavlović S, Čemerikić-Martinović V. JAK2V617F mutacija kod bolesnika sa B ćelijskom hroničnom limfocitnom leukemijom i prefibrotičkom primarnom mijelofibrozom. in Srpski arhiv za celokupno lekarstvo. 2015;143(11-12):739-743.
doi:10.2298/SARH1512739R .
Ristić, Slobodan, Radojković, Milica, Kostić, Tatjana, Spasovski, Vesna, Pavlović, Sonja, Čemerikić-Martinović, Vesna, "JAK2V617F mutacija kod bolesnika sa B ćelijskom hroničnom limfocitnom leukemijom i prefibrotičkom primarnom mijelofibrozom" in Srpski arhiv za celokupno lekarstvo, 143, no. 11-12 (2015):739-743,
https://doi.org/10.2298/SARH1512739R . .
1
1

Ekspresija Bcl2 gena kod pacijenata sa hroničnom limfocitnom leukemijom

Vučićević, Ksenija; Jakovljević, Vladimir; Sretenović, Jasmina; Tošić, Nataša; Kostić, Tatjana; Glumac, Irena; Čolović, Milica; Čolović, Nataša; Pavlović, Sonja; Karan-Đurašević, Teodora

(Univerzitet u Kragujevcu - Fakultet medicinskih nauka, Kragujevac, 2015)

TY  - JOUR
AU  - Vučićević, Ksenija
AU  - Jakovljević, Vladimir
AU  - Sretenović, Jasmina
AU  - Tošić, Nataša
AU  - Kostić, Tatjana
AU  - Glumac, Irena
AU  - Čolović, Milica
AU  - Čolović, Nataša
AU  - Pavlović, Sonja
AU  - Karan-Đurašević, Teodora
PY  - 2015
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/847
AB  - Hronična limfocitna leukemija (HLL) se manifestuje kao klonska ekspanzija zrelih B limfocita, čija se akumulacija pripisuje prvenstveno poremećajima procesa apoptoze. U HLL su uočene genetičke promene i aberantna ekspresija različitih članova Bcl2 genske familije, koji imaju ključnu ulogu u regulaciji unutrašnjeg, mitohondrijskog puta aktivacije apoptoze. U ovom radu je analizirana ekspresija anti-apoptotskog Bcl2 gena u grupi od 58 pacijenata obolelih od HLL. Metodom kvantitativnog RT-PCRa detektovana je povišena ekspresija Bcl2 mRNA u HLL uzorcima u odnosu na kontrolne uzorke (p= lt 0.001). 'Receiver operating characteristic' (ROC) analiza je pokazala da nivo ekspresije Bcl2 ima visoku moć diskriminacije između pacijenata i zdravih kontrola (A=0.98, 95% CI=0.95-1.009, p lt 0.0001).
AB  - Chronic lymphocytic leukaemia (CLL) manifests as clonal expansion of mature B lymphocytes, whose accumulation is primarily attributed to the dysregulation of apoptosis. Aberrant expression, as well as genetic alterations within various Bcl2 family members and central regulators of the intrinsic, mitochondriamediated apoptotic pathway all hasve been observed in CLL. Here, we report the expression analysis of the anti-apoptotic Bcl2 gene in a cohort of 58 CLL patients. Quantitative reverse-transcriptase polymerase chain reaction (qRT-PCR) analysis revealed a significant overexpression of Bcl2 mRNA in CLL samples compared to control samples (p= lt 0.001). Receiver operating characteristic (ROC) analysis showed that the level of Bcl2 expression exerts a high discriminatory power between patients and healthy subjects (A=0.98, 95% CI=0.95-1.009, p lt 0.0001).
PB  - Univerzitet u Kragujevcu - Fakultet medicinskih nauka, Kragujevac
T2  - Serbian Journal of Experimental and Clinical Research
T1  - Ekspresija Bcl2 gena kod pacijenata sa hroničnom limfocitnom leukemijom
T1  - Expression of the Bcl2 gene in chronic lymphocytic leukaemia patients
EP  - 191
IS  - 3
SP  - 187
VL  - 16
DO  - 10.1515/SJECR-2015-0024
ER  - 
@article{
author = "Vučićević, Ksenija and Jakovljević, Vladimir and Sretenović, Jasmina and Tošić, Nataša and Kostić, Tatjana and Glumac, Irena and Čolović, Milica and Čolović, Nataša and Pavlović, Sonja and Karan-Đurašević, Teodora",
year = "2015",
abstract = "Hronična limfocitna leukemija (HLL) se manifestuje kao klonska ekspanzija zrelih B limfocita, čija se akumulacija pripisuje prvenstveno poremećajima procesa apoptoze. U HLL su uočene genetičke promene i aberantna ekspresija različitih članova Bcl2 genske familije, koji imaju ključnu ulogu u regulaciji unutrašnjeg, mitohondrijskog puta aktivacije apoptoze. U ovom radu je analizirana ekspresija anti-apoptotskog Bcl2 gena u grupi od 58 pacijenata obolelih od HLL. Metodom kvantitativnog RT-PCRa detektovana je povišena ekspresija Bcl2 mRNA u HLL uzorcima u odnosu na kontrolne uzorke (p= lt 0.001). 'Receiver operating characteristic' (ROC) analiza je pokazala da nivo ekspresije Bcl2 ima visoku moć diskriminacije između pacijenata i zdravih kontrola (A=0.98, 95% CI=0.95-1.009, p lt 0.0001)., Chronic lymphocytic leukaemia (CLL) manifests as clonal expansion of mature B lymphocytes, whose accumulation is primarily attributed to the dysregulation of apoptosis. Aberrant expression, as well as genetic alterations within various Bcl2 family members and central regulators of the intrinsic, mitochondriamediated apoptotic pathway all hasve been observed in CLL. Here, we report the expression analysis of the anti-apoptotic Bcl2 gene in a cohort of 58 CLL patients. Quantitative reverse-transcriptase polymerase chain reaction (qRT-PCR) analysis revealed a significant overexpression of Bcl2 mRNA in CLL samples compared to control samples (p= lt 0.001). Receiver operating characteristic (ROC) analysis showed that the level of Bcl2 expression exerts a high discriminatory power between patients and healthy subjects (A=0.98, 95% CI=0.95-1.009, p lt 0.0001).",
publisher = "Univerzitet u Kragujevcu - Fakultet medicinskih nauka, Kragujevac",
journal = "Serbian Journal of Experimental and Clinical Research",
title = "Ekspresija Bcl2 gena kod pacijenata sa hroničnom limfocitnom leukemijom, Expression of the Bcl2 gene in chronic lymphocytic leukaemia patients",
pages = "191-187",
number = "3",
volume = "16",
doi = "10.1515/SJECR-2015-0024"
}
Vučićević, K., Jakovljević, V., Sretenović, J., Tošić, N., Kostić, T., Glumac, I., Čolović, M., Čolović, N., Pavlović, S.,& Karan-Đurašević, T.. (2015). Ekspresija Bcl2 gena kod pacijenata sa hroničnom limfocitnom leukemijom. in Serbian Journal of Experimental and Clinical Research
Univerzitet u Kragujevcu - Fakultet medicinskih nauka, Kragujevac., 16(3), 187-191.
https://doi.org/10.1515/SJECR-2015-0024
Vučićević K, Jakovljević V, Sretenović J, Tošić N, Kostić T, Glumac I, Čolović M, Čolović N, Pavlović S, Karan-Đurašević T. Ekspresija Bcl2 gena kod pacijenata sa hroničnom limfocitnom leukemijom. in Serbian Journal of Experimental and Clinical Research. 2015;16(3):187-191.
doi:10.1515/SJECR-2015-0024 .
Vučićević, Ksenija, Jakovljević, Vladimir, Sretenović, Jasmina, Tošić, Nataša, Kostić, Tatjana, Glumac, Irena, Čolović, Milica, Čolović, Nataša, Pavlović, Sonja, Karan-Đurašević, Teodora, "Ekspresija Bcl2 gena kod pacijenata sa hroničnom limfocitnom leukemijom" in Serbian Journal of Experimental and Clinical Research, 16, no. 3 (2015):187-191,
https://doi.org/10.1515/SJECR-2015-0024 . .
1
2

Prognostic impact of wt1 gene expression quantification during minimal residual disease monitoring of acute promyelocytic leukemia

Mitrović, M.; Tošić, Nataša; Suvajdžić, Nada; Djunić, I.; Vidović, A.; Virijević, M.; Čolović, Nataša; Glumac, Irena; Kostić, Tatjana ; Pavlović, Sonja; Elezović, I.; Tomin, D.

(Ferrata Storti Foundation, Pavia, 2015)

TY  - CONF
AU  - Mitrović, M.
AU  - Tošić, Nataša
AU  - Suvajdžić, Nada
AU  - Djunić, I.
AU  - Vidović, A.
AU  - Virijević, M.
AU  - Čolović, Nataša
AU  - Glumac, Irena
AU  - Kostić, Tatjana 
AU  - Pavlović, Sonja
AU  - Elezović, I.
AU  - Tomin, D.
PY  - 2015
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/826
PB  - Ferrata Storti Foundation, Pavia
C3  - Haematologica-The Hematology Journal
T1  - Prognostic impact of wt1 gene expression quantification during minimal residual disease monitoring of acute promyelocytic leukemia
EP  - 378
SP  - 377
VL  - 100
UR  - https://hdl.handle.net/21.15107/rcub_imagine_826
ER  - 
@conference{
author = "Mitrović, M. and Tošić, Nataša and Suvajdžić, Nada and Djunić, I. and Vidović, A. and Virijević, M. and Čolović, Nataša and Glumac, Irena and Kostić, Tatjana  and Pavlović, Sonja and Elezović, I. and Tomin, D.",
year = "2015",
publisher = "Ferrata Storti Foundation, Pavia",
journal = "Haematologica-The Hematology Journal",
title = "Prognostic impact of wt1 gene expression quantification during minimal residual disease monitoring of acute promyelocytic leukemia",
pages = "378-377",
volume = "100",
url = "https://hdl.handle.net/21.15107/rcub_imagine_826"
}
Mitrović, M., Tošić, N., Suvajdžić, N., Djunić, I., Vidović, A., Virijević, M., Čolović, N., Glumac, I., Kostić, T., Pavlović, S., Elezović, I.,& Tomin, D.. (2015). Prognostic impact of wt1 gene expression quantification during minimal residual disease monitoring of acute promyelocytic leukemia. in Haematologica-The Hematology Journal
Ferrata Storti Foundation, Pavia., 100, 377-378.
https://hdl.handle.net/21.15107/rcub_imagine_826
Mitrović M, Tošić N, Suvajdžić N, Djunić I, Vidović A, Virijević M, Čolović N, Glumac I, Kostić T, Pavlović S, Elezović I, Tomin D. Prognostic impact of wt1 gene expression quantification during minimal residual disease monitoring of acute promyelocytic leukemia. in Haematologica-The Hematology Journal. 2015;100:377-378.
https://hdl.handle.net/21.15107/rcub_imagine_826 .
Mitrović, M., Tošić, Nataša, Suvajdžić, Nada, Djunić, I., Vidović, A., Virijević, M., Čolović, Nataša, Glumac, Irena, Kostić, Tatjana , Pavlović, Sonja, Elezović, I., Tomin, D., "Prognostic impact of wt1 gene expression quantification during minimal residual disease monitoring of acute promyelocytic leukemia" in Haematologica-The Hematology Journal, 100 (2015):377-378,
https://hdl.handle.net/21.15107/rcub_imagine_826 .

HLA genotyping in pediatric celiac disease patients

Stanković, Biljana; Radlović, Nedeljko; Leković, Zoran; Ristić, Dragana; Radlović, Vladimir; Nikević, Gordana; Kotur, Nikola; Vucicević, Ksenija; Kostić, Tatjana; Pavlović, Sonja; Zukić, Branka

(Assoc Basic Medical Sci Federation Bosnia & Herzegovina Sarajevo, Cekalusa, 2014)

TY  - JOUR
AU  - Stanković, Biljana
AU  - Radlović, Nedeljko
AU  - Leković, Zoran
AU  - Ristić, Dragana
AU  - Radlović, Vladimir
AU  - Nikević, Gordana
AU  - Kotur, Nikola
AU  - Vucicević, Ksenija
AU  - Kostić, Tatjana
AU  - Pavlović, Sonja
AU  - Zukić, Branka
PY  - 2014
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/733
AB  - Celiac disease (CD) is a chronic inflammatory disease in the small intestine triggered by gluten uptake that occurs in genetically susceptible individuals. HLA-DQ2 protein encoded by HLA-DQA1*05 and DQB1*02 alleles is found in 9o-95% of CD patients. All of the remaining patients carry HLA-DQ8 protein encoded by HLA-DQA1*03 and DQB1*03:02 alleles. Specific HLA-DQ genotypes define different risk for CD incidence. Presence of susceptible HLA-DQ genotypes does not predict certain disease development, but their absence makes CD very unlikely, close to 100%. Here we presented for the first time the distribution of HLA-DQ genotypes in the group of pediatric celiac patients from the University Children's Hospital, Belgrade, Serbia and estimated risk for CD development that these genotypes confer. Seventy three celiac disease patients and 62 healthy individuals underwent genotyping for DQA1, DQB1 alleles and DRB1 allele. 94.5% of patients carried alleles that encode DQ2 protein variant and 2.7% carried alleles that encode DQ8 protein variant. Two patients carried single DQB1 *02 allele. No patients were negative for all the alleles predisposing to CD. The highest HLA-DQ genotype risk for CD development was found in group of patients homozygous for DQ2.5 haplotype, followed by the group of heterozygous carriers of DQ2.5 haplotype in combination with DQB1*02 allele within the other haplotype. The lowest risk was observed in carriers of a single copy of DQB1*02 or DQA1*05 allele or other non-predisposing alleles. HLA genotyping, more informative than serological testing commonly used, proved to be a useful diagnostic tool for excluding CD development.
PB  - Assoc Basic Medical Sci Federation Bosnia & Herzegovina Sarajevo, Cekalusa
T2  - Bosnian Journal of Basic Medical Sciences
T1  - HLA genotyping in pediatric celiac disease patients
EP  - 176
IS  - 3
SP  - 171
VL  - 14
DO  - 10.17305/bjbms.2014.3.28
ER  - 
@article{
author = "Stanković, Biljana and Radlović, Nedeljko and Leković, Zoran and Ristić, Dragana and Radlović, Vladimir and Nikević, Gordana and Kotur, Nikola and Vucicević, Ksenija and Kostić, Tatjana and Pavlović, Sonja and Zukić, Branka",
year = "2014",
abstract = "Celiac disease (CD) is a chronic inflammatory disease in the small intestine triggered by gluten uptake that occurs in genetically susceptible individuals. HLA-DQ2 protein encoded by HLA-DQA1*05 and DQB1*02 alleles is found in 9o-95% of CD patients. All of the remaining patients carry HLA-DQ8 protein encoded by HLA-DQA1*03 and DQB1*03:02 alleles. Specific HLA-DQ genotypes define different risk for CD incidence. Presence of susceptible HLA-DQ genotypes does not predict certain disease development, but their absence makes CD very unlikely, close to 100%. Here we presented for the first time the distribution of HLA-DQ genotypes in the group of pediatric celiac patients from the University Children's Hospital, Belgrade, Serbia and estimated risk for CD development that these genotypes confer. Seventy three celiac disease patients and 62 healthy individuals underwent genotyping for DQA1, DQB1 alleles and DRB1 allele. 94.5% of patients carried alleles that encode DQ2 protein variant and 2.7% carried alleles that encode DQ8 protein variant. Two patients carried single DQB1 *02 allele. No patients were negative for all the alleles predisposing to CD. The highest HLA-DQ genotype risk for CD development was found in group of patients homozygous for DQ2.5 haplotype, followed by the group of heterozygous carriers of DQ2.5 haplotype in combination with DQB1*02 allele within the other haplotype. The lowest risk was observed in carriers of a single copy of DQB1*02 or DQA1*05 allele or other non-predisposing alleles. HLA genotyping, more informative than serological testing commonly used, proved to be a useful diagnostic tool for excluding CD development.",
publisher = "Assoc Basic Medical Sci Federation Bosnia & Herzegovina Sarajevo, Cekalusa",
journal = "Bosnian Journal of Basic Medical Sciences",
title = "HLA genotyping in pediatric celiac disease patients",
pages = "176-171",
number = "3",
volume = "14",
doi = "10.17305/bjbms.2014.3.28"
}
Stanković, B., Radlović, N., Leković, Z., Ristić, D., Radlović, V., Nikević, G., Kotur, N., Vucicević, K., Kostić, T., Pavlović, S.,& Zukić, B.. (2014). HLA genotyping in pediatric celiac disease patients. in Bosnian Journal of Basic Medical Sciences
Assoc Basic Medical Sci Federation Bosnia & Herzegovina Sarajevo, Cekalusa., 14(3), 171-176.
https://doi.org/10.17305/bjbms.2014.3.28
Stanković B, Radlović N, Leković Z, Ristić D, Radlović V, Nikević G, Kotur N, Vucicević K, Kostić T, Pavlović S, Zukić B. HLA genotyping in pediatric celiac disease patients. in Bosnian Journal of Basic Medical Sciences. 2014;14(3):171-176.
doi:10.17305/bjbms.2014.3.28 .
Stanković, Biljana, Radlović, Nedeljko, Leković, Zoran, Ristić, Dragana, Radlović, Vladimir, Nikević, Gordana, Kotur, Nikola, Vucicević, Ksenija, Kostić, Tatjana, Pavlović, Sonja, Zukić, Branka, "HLA genotyping in pediatric celiac disease patients" in Bosnian Journal of Basic Medical Sciences, 14, no. 3 (2014):171-176,
https://doi.org/10.17305/bjbms.2014.3.28 . .
2
25
9
21

Adverse prognostic significance of wilms tumor gene 1 overexpression in acute promyelocytic leukemia

Mitrović, M.; Tošić, Nataša; Suvajdžić, Nada; Djunić, I.; Vidović, A.; Virijević, M.; Čolović, Nataša; Kostić, Tatjana ; Glumac, Irena; Pavlović, Sonja; Elezović, I.; Tomin, D.

(Ferrata Storti Foundation, Pavia, 2014)

TY  - CONF
AU  - Mitrović, M.
AU  - Tošić, Nataša
AU  - Suvajdžić, Nada
AU  - Djunić, I.
AU  - Vidović, A.
AU  - Virijević, M.
AU  - Čolović, Nataša
AU  - Kostić, Tatjana 
AU  - Glumac, Irena
AU  - Pavlović, Sonja
AU  - Elezović, I.
AU  - Tomin, D.
PY  - 2014
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/744
PB  - Ferrata Storti Foundation, Pavia
C3  - Haematologica-The Hematology Journal
T1  - Adverse prognostic significance of wilms tumor gene 1 overexpression in acute promyelocytic leukemia
EP  - 575
SP  - 575
VL  - 99
UR  - https://hdl.handle.net/21.15107/rcub_imagine_744
ER  - 
@conference{
author = "Mitrović, M. and Tošić, Nataša and Suvajdžić, Nada and Djunić, I. and Vidović, A. and Virijević, M. and Čolović, Nataša and Kostić, Tatjana  and Glumac, Irena and Pavlović, Sonja and Elezović, I. and Tomin, D.",
year = "2014",
publisher = "Ferrata Storti Foundation, Pavia",
journal = "Haematologica-The Hematology Journal",
title = "Adverse prognostic significance of wilms tumor gene 1 overexpression in acute promyelocytic leukemia",
pages = "575-575",
volume = "99",
url = "https://hdl.handle.net/21.15107/rcub_imagine_744"
}
Mitrović, M., Tošić, N., Suvajdžić, N., Djunić, I., Vidović, A., Virijević, M., Čolović, N., Kostić, T., Glumac, I., Pavlović, S., Elezović, I.,& Tomin, D.. (2014). Adverse prognostic significance of wilms tumor gene 1 overexpression in acute promyelocytic leukemia. in Haematologica-The Hematology Journal
Ferrata Storti Foundation, Pavia., 99, 575-575.
https://hdl.handle.net/21.15107/rcub_imagine_744
Mitrović M, Tošić N, Suvajdžić N, Djunić I, Vidović A, Virijević M, Čolović N, Kostić T, Glumac I, Pavlović S, Elezović I, Tomin D. Adverse prognostic significance of wilms tumor gene 1 overexpression in acute promyelocytic leukemia. in Haematologica-The Hematology Journal. 2014;99:575-575.
https://hdl.handle.net/21.15107/rcub_imagine_744 .
Mitrović, M., Tošić, Nataša, Suvajdžić, Nada, Djunić, I., Vidović, A., Virijević, M., Čolović, Nataša, Kostić, Tatjana , Glumac, Irena, Pavlović, Sonja, Elezović, I., Tomin, D., "Adverse prognostic significance of wilms tumor gene 1 overexpression in acute promyelocytic leukemia" in Haematologica-The Hematology Journal, 99 (2014):575-575,
https://hdl.handle.net/21.15107/rcub_imagine_744 .

Gammopathy and B lymphocyte clonality in patients with Gaucher type I disease

Rodić, Predrag; Pavlović, Sonja; Kostić, Tatjana; Suvajdžić-Vuković, Nada; Đorđević, Maja; Sumarac, Zorica; Dajak, Marijana; Bonaci-Nikolić, Branka; Janić, Dragana

(Academic Press Inc Elsevier Science, San Diego, 2013)

TY  - JOUR
AU  - Rodić, Predrag
AU  - Pavlović, Sonja
AU  - Kostić, Tatjana
AU  - Suvajdžić-Vuković, Nada
AU  - Đorđević, Maja
AU  - Sumarac, Zorica
AU  - Dajak, Marijana
AU  - Bonaci-Nikolić, Branka
AU  - Janić, Dragana
PY  - 2013
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/621
AB  - Introduction: We evaluated a novel approach for investigation of lymphocyte dysregulation in Gaucher patients by including determination of IgH and TCR gene rearrangements together with levels of immunoglobulins, natural autoantibodies as well as presence of monoclonal protein. Materials and methods: Measurement of serum immunoglobulins, monoclonal immunoglobulins, selected autoantibodies, as well as analysis of immunoglobulin heavy chain and T cell receptor gene rearrangements. Results: Immunoglobulin disorder was detected in 29.6% patients, 40.7% demonstrated presence of B cell clonality and 44.4% demonstrated presence of autoantibodies. In five patients in our series, the presence of IgH gene rearrangement was the only detectable indicator of B cell dysfunction. TCR gene rearrangements were not found in any of the patients. Conclusion: Based on our results, we propose IgH gene rearrangements as a new biomarker for investigation of B cell dysfunction occurring as a complication of Gaucher disease.
PB  - Academic Press Inc Elsevier Science, San Diego
T2  - Blood Cells Molecules and Diseases
T1  - Gammopathy and B lymphocyte clonality in patients with Gaucher type I disease
EP  - 225
IS  - 3
SP  - 222
VL  - 50
DO  - 10.1016/j.bcmd.2012.11.012
ER  - 
@article{
author = "Rodić, Predrag and Pavlović, Sonja and Kostić, Tatjana and Suvajdžić-Vuković, Nada and Đorđević, Maja and Sumarac, Zorica and Dajak, Marijana and Bonaci-Nikolić, Branka and Janić, Dragana",
year = "2013",
abstract = "Introduction: We evaluated a novel approach for investigation of lymphocyte dysregulation in Gaucher patients by including determination of IgH and TCR gene rearrangements together with levels of immunoglobulins, natural autoantibodies as well as presence of monoclonal protein. Materials and methods: Measurement of serum immunoglobulins, monoclonal immunoglobulins, selected autoantibodies, as well as analysis of immunoglobulin heavy chain and T cell receptor gene rearrangements. Results: Immunoglobulin disorder was detected in 29.6% patients, 40.7% demonstrated presence of B cell clonality and 44.4% demonstrated presence of autoantibodies. In five patients in our series, the presence of IgH gene rearrangement was the only detectable indicator of B cell dysfunction. TCR gene rearrangements were not found in any of the patients. Conclusion: Based on our results, we propose IgH gene rearrangements as a new biomarker for investigation of B cell dysfunction occurring as a complication of Gaucher disease.",
publisher = "Academic Press Inc Elsevier Science, San Diego",
journal = "Blood Cells Molecules and Diseases",
title = "Gammopathy and B lymphocyte clonality in patients with Gaucher type I disease",
pages = "225-222",
number = "3",
volume = "50",
doi = "10.1016/j.bcmd.2012.11.012"
}
Rodić, P., Pavlović, S., Kostić, T., Suvajdžić-Vuković, N., Đorđević, M., Sumarac, Z., Dajak, M., Bonaci-Nikolić, B.,& Janić, D.. (2013). Gammopathy and B lymphocyte clonality in patients with Gaucher type I disease. in Blood Cells Molecules and Diseases
Academic Press Inc Elsevier Science, San Diego., 50(3), 222-225.
https://doi.org/10.1016/j.bcmd.2012.11.012
Rodić P, Pavlović S, Kostić T, Suvajdžić-Vuković N, Đorđević M, Sumarac Z, Dajak M, Bonaci-Nikolić B, Janić D. Gammopathy and B lymphocyte clonality in patients with Gaucher type I disease. in Blood Cells Molecules and Diseases. 2013;50(3):222-225.
doi:10.1016/j.bcmd.2012.11.012 .
Rodić, Predrag, Pavlović, Sonja, Kostić, Tatjana, Suvajdžić-Vuković, Nada, Đorđević, Maja, Sumarac, Zorica, Dajak, Marijana, Bonaci-Nikolić, Branka, Janić, Dragana, "Gammopathy and B lymphocyte clonality in patients with Gaucher type I disease" in Blood Cells Molecules and Diseases, 50, no. 3 (2013):222-225,
https://doi.org/10.1016/j.bcmd.2012.11.012 . .
6
9
5
10

Adverse prognostic significance of FLT3 mutations in acute promyelocytic leukemia

Mitrović, M.; Suvajdžić, Nada; Tošić, Nataša; Bogdanović, A.; Djunić, I.; Sretenović, A.; Vidović, A.; Virijević, M.; Čolović, Nataša; Kostić, Tatjana ; Karan-Đurašević, Teodora; Glumac, Irena; Spasovski, Vesna; Pavlović, Sonja; Elezović, I.; Tomin, D.

(Ferrata Storti Foundation, Pavia, 2013)

TY  - CONF
AU  - Mitrović, M.
AU  - Suvajdžić, Nada
AU  - Tošić, Nataša
AU  - Bogdanović, A.
AU  - Djunić, I.
AU  - Sretenović, A.
AU  - Vidović, A.
AU  - Virijević, M.
AU  - Čolović, Nataša
AU  - Kostić, Tatjana 
AU  - Karan-Đurašević, Teodora
AU  - Glumac, Irena
AU  - Spasovski, Vesna
AU  - Pavlović, Sonja
AU  - Elezović, I.
AU  - Tomin, D.
PY  - 2013
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/680
PB  - Ferrata Storti Foundation, Pavia
C3  - Haematologica-The Hematology Journal
T1  - Adverse prognostic significance of FLT3 mutations in acute promyelocytic leukemia
EP  - 283
SP  - 282
VL  - 98
UR  - https://hdl.handle.net/21.15107/rcub_imagine_680
ER  - 
@conference{
author = "Mitrović, M. and Suvajdžić, Nada and Tošić, Nataša and Bogdanović, A. and Djunić, I. and Sretenović, A. and Vidović, A. and Virijević, M. and Čolović, Nataša and Kostić, Tatjana  and Karan-Đurašević, Teodora and Glumac, Irena and Spasovski, Vesna and Pavlović, Sonja and Elezović, I. and Tomin, D.",
year = "2013",
publisher = "Ferrata Storti Foundation, Pavia",
journal = "Haematologica-The Hematology Journal",
title = "Adverse prognostic significance of FLT3 mutations in acute promyelocytic leukemia",
pages = "283-282",
volume = "98",
url = "https://hdl.handle.net/21.15107/rcub_imagine_680"
}
Mitrović, M., Suvajdžić, N., Tošić, N., Bogdanović, A., Djunić, I., Sretenović, A., Vidović, A., Virijević, M., Čolović, N., Kostić, T., Karan-Đurašević, T., Glumac, I., Spasovski, V., Pavlović, S., Elezović, I.,& Tomin, D.. (2013). Adverse prognostic significance of FLT3 mutations in acute promyelocytic leukemia. in Haematologica-The Hematology Journal
Ferrata Storti Foundation, Pavia., 98, 282-283.
https://hdl.handle.net/21.15107/rcub_imagine_680
Mitrović M, Suvajdžić N, Tošić N, Bogdanović A, Djunić I, Sretenović A, Vidović A, Virijević M, Čolović N, Kostić T, Karan-Đurašević T, Glumac I, Spasovski V, Pavlović S, Elezović I, Tomin D. Adverse prognostic significance of FLT3 mutations in acute promyelocytic leukemia. in Haematologica-The Hematology Journal. 2013;98:282-283.
https://hdl.handle.net/21.15107/rcub_imagine_680 .
Mitrović, M., Suvajdžić, Nada, Tošić, Nataša, Bogdanović, A., Djunić, I., Sretenović, A., Vidović, A., Virijević, M., Čolović, Nataša, Kostić, Tatjana , Karan-Đurašević, Teodora, Glumac, Irena, Spasovski, Vesna, Pavlović, Sonja, Elezović, I., Tomin, D., "Adverse prognostic significance of FLT3 mutations in acute promyelocytic leukemia" in Haematologica-The Hematology Journal, 98 (2013):282-283,
https://hdl.handle.net/21.15107/rcub_imagine_680 .