Tošić, Nataša

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Authority KeyName Variants
orcid::0000-0002-1293-6215
  • Tošić, Nataša (114)
  • Tošic, Natasa (1)
  • Tošić, Nataša (1)
Projects
Rare Diseases:Molecular Pathophysiology, Diagnostic and Therapeutic Modalities and Social, Ethical and Legal Aspects info:eu-repo/grantAgreement/MESTD/inst-2020/200042/RS//
Strukturalni elementi genoma u modulaciji fenotipa Strengthening the Research Potential of IMGGE through Reinforcement of Biomedical Science of Rare Diseases in Serbia - en route for innovation
Molecular, biochemical and immunological tumor diagnosis Austrian Science Fund (FWF) [P 23257] Funding Source: researchfish
Molekularno genetski markeri klonskog preobražaja matičnih ćelija hematopoeze Fondazione Cariplo
Trophoblast and extraembryonic fetal cells: plasticity, differentiation factors and in vitro modulation of functional characteristics Italian Society of Experimental Hematology (SIES)
MPN Research Foundation Acknowledgments This work has been funded by the Ministry of Education and Science, Republic of Serbia, grant No. III 41004.
AIRC [9034, MIUR-20084XBENM_002] Associazione Italiana per la Ricerca sul Cancro (AIRC, Milano)
Associazione Italiana per la Ricerca sul Cancro (AIRC, Milano) [1005] Associazione Italiana per la Ricerca sul Cancro (AIRC, Milano) [1005, IG 9034]
Austrian Science Fund Austrian Science Fund (FWF) [P 21401] Funding Source: researchfish
Austrian Science Fund (FWF) [P23257-B12] Austrian Science Fund [P23257-B12]
Dana Dvorakova's laboratory [MSM0021622430] EB: 451-03-68/2020-14/200042]
European Commission European Commission, EU-FP7-REGPOT-316088, 2013-2016
European Social Fund and National Resources - (EPEAEK II) PYTHAGORAS II Fondazione Berlucchi, Brescia, Italy
Genes and molecular mechanisms promoting probiotic activity of lactic acid bacteria from Western Balkan Studying signal transduction pathways and epigenetic mechanisms that control human SOX genes expression: further insight into their roles in cell fate determination and differentiation
Ethnogenesis of the Serbs during the middle ages: a comparative analysis of the historical-cultural heritage, genetic material and artefacts of material culture from the aspect of analytical chemistry Izučavanje regulacije ekspresije i funkcije humanih SOX gena

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 . .

Germline Variants in Cancer Predisposition Genes in Pediatric Patients with Central Nervous System Tumors

Jovanović, Aleksa; Tošić, Nataša; Marjanović, Irena; Komazec, Jovana; Zukić, Branka; Nikitović, Marina; Ilić, Rosanda; Grujičić, Danica; Janić, Dragana; Pavlović, Sonja

(2023)

TY  - JOUR
AU  - Jovanović, Aleksa
AU  - Tošić, Nataša
AU  - Marjanović, Irena
AU  - Komazec, Jovana
AU  - Zukić, Branka
AU  - Nikitović, Marina
AU  - Ilić, Rosanda
AU  - Grujičić, Danica
AU  - Janić, Dragana
AU  - Pavlović, Sonja
PY  - 2023
UR  - https://www.mdpi.com/1422-0067/24/24/17387
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/2279
AB  - Central nervous system (CNS) tumors comprise around 20% of childhood malignancies. Germline variants in cancer predisposition genes (CPGs) are found in approximately 10% of pediatric patients with CNS tumors. This study aimed to characterize variants in CPGs in pediatric patients with CNS tumors and correlate these findings with clinically relevant data. Genomic DNA was isolated from the peripheral blood of 51 pediatric patients and further analyzed by the next-generation sequencing approach. Bioinformatic analysis was done using an “in-house” gene list panel, which included 144 genes related to pediatric brain tumors, and the gene list panel Neoplasm (HP:0002664). Our study found that 27% of pediatric patients with CNS tumors have a germline variant in some of the known CPGs, like ALK, APC, CHEK2, ELP1, MLH1, MSH2, NF1, NF2 and TP53. This study represents the first comprehensive evaluation of germline variants in pediatric patients with CNS tumors in the Western Balkans region. Our results indicate the necessity of genomic research to reveal the genetic basis of pediatric CNS tumors, as well as to define targets for the application and development of innovative therapeutics that form the basis of the upcoming era of personalized medicine.
T2  - International Journal of Molecular Sciences
T1  - Germline Variants in Cancer Predisposition Genes in Pediatric Patients with Central Nervous System Tumors
IS  - 24
SP  - 17387
VL  - 24
DO  - 10.3390/ijms242417387
ER  - 
@article{
author = "Jovanović, Aleksa and Tošić, Nataša and Marjanović, Irena and Komazec, Jovana and Zukić, Branka and Nikitović, Marina and Ilić, Rosanda and Grujičić, Danica and Janić, Dragana and Pavlović, Sonja",
year = "2023",
abstract = "Central nervous system (CNS) tumors comprise around 20% of childhood malignancies. Germline variants in cancer predisposition genes (CPGs) are found in approximately 10% of pediatric patients with CNS tumors. This study aimed to characterize variants in CPGs in pediatric patients with CNS tumors and correlate these findings with clinically relevant data. Genomic DNA was isolated from the peripheral blood of 51 pediatric patients and further analyzed by the next-generation sequencing approach. Bioinformatic analysis was done using an “in-house” gene list panel, which included 144 genes related to pediatric brain tumors, and the gene list panel Neoplasm (HP:0002664). Our study found that 27% of pediatric patients with CNS tumors have a germline variant in some of the known CPGs, like ALK, APC, CHEK2, ELP1, MLH1, MSH2, NF1, NF2 and TP53. This study represents the first comprehensive evaluation of germline variants in pediatric patients with CNS tumors in the Western Balkans region. Our results indicate the necessity of genomic research to reveal the genetic basis of pediatric CNS tumors, as well as to define targets for the application and development of innovative therapeutics that form the basis of the upcoming era of personalized medicine.",
journal = "International Journal of Molecular Sciences",
title = "Germline Variants in Cancer Predisposition Genes in Pediatric Patients with Central Nervous System Tumors",
number = "24",
pages = "17387",
volume = "24",
doi = "10.3390/ijms242417387"
}
Jovanović, A., Tošić, N., Marjanović, I., Komazec, J., Zukić, B., Nikitović, M., Ilić, R., Grujičić, D., Janić, D.,& Pavlović, S.. (2023). Germline Variants in Cancer Predisposition Genes in Pediatric Patients with Central Nervous System Tumors. in International Journal of Molecular Sciences, 24(24), 17387.
https://doi.org/10.3390/ijms242417387
Jovanović A, Tošić N, Marjanović I, Komazec J, Zukić B, Nikitović M, Ilić R, Grujičić D, Janić D, Pavlović S. Germline Variants in Cancer Predisposition Genes in Pediatric Patients with Central Nervous System Tumors. in International Journal of Molecular Sciences. 2023;24(24):17387.
doi:10.3390/ijms242417387 .
Jovanović, Aleksa, Tošić, Nataša, Marjanović, Irena, Komazec, Jovana, Zukić, Branka, Nikitović, Marina, Ilić, Rosanda, Grujičić, Danica, Janić, Dragana, Pavlović, Sonja, "Germline Variants in Cancer Predisposition Genes in Pediatric Patients with Central Nervous System Tumors" in International Journal of Molecular Sciences, 24, no. 24 (2023):17387,
https://doi.org/10.3390/ijms242417387 . .

Expression levels of BCL2, BAX and MDR1 as pharmacotranscriptomic and prognostic markers of prognosis in acute myeloid leukemia

Gašić, Vladimir; Pravdić, Zlatko; Suvajdžić Vuković, Nada; Marjanović, Irena; Karan-Đurašević, Teodora; Pavlović, Sonja; Tošić, Nataša

(Sarajevo : Institute for Genetic Engineering and Biotechnology, University of Sarajevo, 2023)

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

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 .

Prognostic significance of cebpa mutations in patients with normal-karyotype - acute myeloid leukemia

Marjanović, Irena; Kraguljac Kurtović, Nada; Karan-Đurašević, Teodora; Pavlović, Sonja; Tošić, Nataša

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

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

Molecular diagnosis of Fabry disease in patients with chronic renal failure of unknown etiology

Parezanović, Marina; Stojiljković, Maja; Anđelković, Marina; Stevanović, Nina; Spasovski, Vesna; Ugrin, Milena; Komazec, Jovana; Tošić, Nataša; Pavlović, Sonja; Celic, Dejan; Vučenović, Jelica; Skakić, Anita

(Springer Nature, 2023)

TY  - CONF
AU  - Parezanović, Marina
AU  - Stojiljković, Maja
AU  - Anđelković, Marina
AU  - Stevanović, Nina
AU  - Spasovski, Vesna
AU  - Ugrin, Milena
AU  - Komazec, Jovana
AU  - Tošić, Nataša
AU  - Pavlović, Sonja
AU  - Celic, Dejan
AU  - Vučenović, Jelica
AU  - Skakić, Anita
PY  - 2023
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/2277
AB  - Background/Objectives: Fabry disease (FD) is a rare X-linked
disorder caused by variants in the GLA gene leading to the deficiency
of lysosomal α-galactosidase-A and progressive accumulation
of globotriaosylceramide affecting the heart, nervous system,
and kidneys. FD has overlapping phenotypes and often remains
undiagnosed. Therefore, the precise molecular-genetic diagnosis
and the earliest possible treatment are essential to avoid significant
disease progression.
Methods: We analyzed 95 (34 female and 61 male) hemodialysis
patients with clinical suspicion of FD using Sanger sequencing
of all coding exons (7) and flanking intron regions of the GLA
gene, and measured the relative expression of the GLA gene in
available samples.
Results: The genetic analysis revealed 3 patients with a missense
variant (p.Asp313Tyr), and 10 patients with combinations of
non-coding variants, described as complex intronic haplotypes
(CIHs). CIH1 (c.-10C>T, c.370-81_370-77delCAGCC, c.640-16A>G,
c.1000-22C>T), the most frequent haplotype, was detected in 7
(7.4%) patients. Lyso-Gb3 biomarker levels were within the normal
range in each tested patient. However, RT-qPCR analysis revealed
decreased relative expression of GLA gene in PBMC of 2 female
patients with CIH1 and one female patient carrying only c.-10C>T
variant by 9,1%, 7,4%, 46,3%, respectively, pointing out that further
analyses are needed to confirm/exclude FD in these patients.
Conclusion: Because the effects of CIHs are not yet fully
understood, our work highlights the importance of analyzing
intronic regions of the GLA gene as genetic modifiers and the
need to include expression analysis in the diagnostic algorithm.
PB  - Springer Nature
C3  - European Journal of Human Genetic
T1  - Molecular diagnosis of Fabry disease in patients with chronic renal failure of unknown etiology
EP  - 433
IS  - Supplement S1
SP  - 432
VL  - 31
DO  - 10.1038/s41431-023-01339-3
ER  - 
@conference{
author = "Parezanović, Marina and Stojiljković, Maja and Anđelković, Marina and Stevanović, Nina and Spasovski, Vesna and Ugrin, Milena and Komazec, Jovana and Tošić, Nataša and Pavlović, Sonja and Celic, Dejan and Vučenović, Jelica and Skakić, Anita",
year = "2023",
abstract = "Background/Objectives: Fabry disease (FD) is a rare X-linked
disorder caused by variants in the GLA gene leading to the deficiency
of lysosomal α-galactosidase-A and progressive accumulation
of globotriaosylceramide affecting the heart, nervous system,
and kidneys. FD has overlapping phenotypes and often remains
undiagnosed. Therefore, the precise molecular-genetic diagnosis
and the earliest possible treatment are essential to avoid significant
disease progression.
Methods: We analyzed 95 (34 female and 61 male) hemodialysis
patients with clinical suspicion of FD using Sanger sequencing
of all coding exons (7) and flanking intron regions of the GLA
gene, and measured the relative expression of the GLA gene in
available samples.
Results: The genetic analysis revealed 3 patients with a missense
variant (p.Asp313Tyr), and 10 patients with combinations of
non-coding variants, described as complex intronic haplotypes
(CIHs). CIH1 (c.-10C>T, c.370-81_370-77delCAGCC, c.640-16A>G,
c.1000-22C>T), the most frequent haplotype, was detected in 7
(7.4%) patients. Lyso-Gb3 biomarker levels were within the normal
range in each tested patient. However, RT-qPCR analysis revealed
decreased relative expression of GLA gene in PBMC of 2 female
patients with CIH1 and one female patient carrying only c.-10C>T
variant by 9,1%, 7,4%, 46,3%, respectively, pointing out that further
analyses are needed to confirm/exclude FD in these patients.
Conclusion: Because the effects of CIHs are not yet fully
understood, our work highlights the importance of analyzing
intronic regions of the GLA gene as genetic modifiers and the
need to include expression analysis in the diagnostic algorithm.",
publisher = "Springer Nature",
journal = "European Journal of Human Genetic",
title = "Molecular diagnosis of Fabry disease in patients with chronic renal failure of unknown etiology",
pages = "433-432",
number = "Supplement S1",
volume = "31",
doi = "10.1038/s41431-023-01339-3"
}
Parezanović, M., Stojiljković, M., Anđelković, M., Stevanović, N., Spasovski, V., Ugrin, M., Komazec, J., Tošić, N., Pavlović, S., Celic, D., Vučenović, J.,& Skakić, A.. (2023). Molecular diagnosis of Fabry disease in patients with chronic renal failure of unknown etiology. in European Journal of Human Genetic
Springer Nature., 31(Supplement S1), 432-433.
https://doi.org/10.1038/s41431-023-01339-3
Parezanović M, Stojiljković M, Anđelković M, Stevanović N, Spasovski V, Ugrin M, Komazec J, Tošić N, Pavlović S, Celic D, Vučenović J, Skakić A. Molecular diagnosis of Fabry disease in patients with chronic renal failure of unknown etiology. in European Journal of Human Genetic. 2023;31(Supplement S1):432-433.
doi:10.1038/s41431-023-01339-3 .
Parezanović, Marina, Stojiljković, Maja, Anđelković, Marina, Stevanović, Nina, Spasovski, Vesna, Ugrin, Milena, Komazec, Jovana, Tošić, Nataša, Pavlović, Sonja, Celic, Dejan, Vučenović, Jelica, Skakić, Anita, "Molecular diagnosis of Fabry disease in patients with chronic renal failure of unknown etiology" in European Journal of Human Genetic, 31, no. Supplement S1 (2023):432-433,
https://doi.org/10.1038/s41431-023-01339-3 . .
1

NUDT15 as potential marker for pharmacogenetic-guided 6-mercaptopurine therapy in children with acute lymphoblastic leukemia in Serbia

Ristivojević, Bojan; Kotur, Nikola; Tošić, Nataša; Stanković, Biljana; Gašić, Vladimir; Pavlović, Đorđe; Jelovac, Marina; Milošević, Goran; Pavlović, Sonja; Zukić, Branka

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

TY  - CONF
AU  - Ristivojević, Bojan
AU  - Kotur, Nikola
AU  - Tošić, Nataša
AU  - Stanković, Biljana
AU  - Gašić, Vladimir
AU  - Pavlović, Đorđe
AU  - Jelovac, Marina
AU  - Milošević, Goran
AU  - Pavlović, Sonja
AU  - Zukić, Branka
PY  - 2023
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/2128
AB  - Introduction: The NUDT15 is new pharmacogene of importance for 6-mercaptopurine therapy, given to
children with acute lymphoblastic leukemia (ALL). The association ofside effectsin children with variants
in NUDT15 are well established in Asian populations, yet the relevance ofthis pharmacogene in European
populationsremainslargely unexplored. The aim of thisstudy wasto identify pharmacogenetic variants
in coding and neighbouring regions of NUDT15 gene and analyse if the expression levels of NUDT15 can
predict the occurence of side effects of 6-mercaptopurine during the maintenance therapy in children
with ALL of Serbian origin.
Methods: The genotyping of coding and neighbouring regions of NUDT15 gene was performed using
PCR and Sangersequencing based technology in 48 children with ALL. NUDT15 expression was analyzed
in mononuclear cells of 24 ALL patients at diagnosis and 6 healthy controls by qRT-PCR, and association
with surogate markers was assessed using adequate statistical methodology.
Results: The genotypig revealed the presence of 5 variantsin NUDT15 (NUDT15(NM_018283.4):c.36A>C,
NUDT15(NM_018283.4):c.158+117C>T,NUDT15(NM_018283.4):c.158+174G>A,NUDT15(NM_018283.4):c.159-
91G>A,NUDT15(NM_018283.4):c.*7G>A), none of them with effects on the expression or the function of
NUDT15 protein. There was no statistically significant association between the expression of NUDT15 at
diagnosis and the surogate markers of side effects (number of episodes of leukopenia (p=0.821), number of weeks without therapy (p=0.507), number of weeks with lower dose (p=0.434), average doses
(p=0.374)) of 6-mercaptopurine during the maintenance therapy.
Conclusion: Presently, NUDT15 cannot be used as a pharmacogene in predicting the toxicity of 6-mercaptopurine terapy in children with ALL in Serbia.
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  - NUDT15 as potential marker for pharmacogenetic-guided 6-mercaptopurine therapy in children with acute lymphoblastic leukemia in Serbia
EP  - 81
SP  - 81
UR  - https://hdl.handle.net/21.15107/rcub_imagine_2128
ER  - 
@conference{
author = "Ristivojević, Bojan and Kotur, Nikola and Tošić, Nataša and Stanković, Biljana and Gašić, Vladimir and Pavlović, Đorđe and Jelovac, Marina and Milošević, Goran and Pavlović, Sonja and Zukić, Branka",
year = "2023",
abstract = "Introduction: The NUDT15 is new pharmacogene of importance for 6-mercaptopurine therapy, given to
children with acute lymphoblastic leukemia (ALL). The association ofside effectsin children with variants
in NUDT15 are well established in Asian populations, yet the relevance ofthis pharmacogene in European
populationsremainslargely unexplored. The aim of thisstudy wasto identify pharmacogenetic variants
in coding and neighbouring regions of NUDT15 gene and analyse if the expression levels of NUDT15 can
predict the occurence of side effects of 6-mercaptopurine during the maintenance therapy in children
with ALL of Serbian origin.
Methods: The genotyping of coding and neighbouring regions of NUDT15 gene was performed using
PCR and Sangersequencing based technology in 48 children with ALL. NUDT15 expression was analyzed
in mononuclear cells of 24 ALL patients at diagnosis and 6 healthy controls by qRT-PCR, and association
with surogate markers was assessed using adequate statistical methodology.
Results: The genotypig revealed the presence of 5 variantsin NUDT15 (NUDT15(NM_018283.4):c.36A>C,
NUDT15(NM_018283.4):c.158+117C>T,NUDT15(NM_018283.4):c.158+174G>A,NUDT15(NM_018283.4):c.159-
91G>A,NUDT15(NM_018283.4):c.*7G>A), none of them with effects on the expression or the function of
NUDT15 protein. There was no statistically significant association between the expression of NUDT15 at
diagnosis and the surogate markers of side effects (number of episodes of leukopenia (p=0.821), number of weeks without therapy (p=0.507), number of weeks with lower dose (p=0.434), average doses
(p=0.374)) of 6-mercaptopurine during the maintenance therapy.
Conclusion: Presently, NUDT15 cannot be used as a pharmacogene in predicting the toxicity of 6-mercaptopurine terapy in children with ALL in Serbia.",
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 = "NUDT15 as potential marker for pharmacogenetic-guided 6-mercaptopurine therapy in children with acute lymphoblastic leukemia in Serbia",
pages = "81-81",
url = "https://hdl.handle.net/21.15107/rcub_imagine_2128"
}
Ristivojević, B., Kotur, N., Tošić, N., Stanković, B., Gašić, V., Pavlović, Đ., Jelovac, M., Milošević, G., Pavlović, S.,& Zukić, B.. (2023). NUDT15 as potential marker for pharmacogenetic-guided 6-mercaptopurine therapy in children with acute lymphoblastic leukemia in Serbia. 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., 81-81.
https://hdl.handle.net/21.15107/rcub_imagine_2128
Ristivojević B, Kotur N, Tošić N, Stanković B, Gašić V, Pavlović Đ, Jelovac M, Milošević G, Pavlović S, Zukić B. NUDT15 as potential marker for pharmacogenetic-guided 6-mercaptopurine therapy in children with acute lymphoblastic leukemia in Serbia. 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;:81-81.
https://hdl.handle.net/21.15107/rcub_imagine_2128 .
Ristivojević, Bojan, Kotur, Nikola, Tošić, Nataša, Stanković, Biljana, Gašić, Vladimir, Pavlović, Đorđe, Jelovac, Marina, Milošević, Goran, Pavlović, Sonja, Zukić, Branka, "NUDT15 as potential marker for pharmacogenetic-guided 6-mercaptopurine therapy in children with acute lymphoblastic leukemia in Serbia" 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):81-81,
https://hdl.handle.net/21.15107/rcub_imagine_2128 .

Expression profiles of long non-coding RNA gas5 and microrna-222 in younger AML patients

Đorđe, Pavlović; Tošić, Nataša; Zukić, Branka; Pravić, Zlatko; Suvajdžić Vuković, Nada; Pavlović, Sonja; Gašić, Vladimir

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

TY  - CONF
AU  - Đorđe, Pavlović
AU  - Tošić, Nataša
AU  - Zukić, Branka
AU  - Pravić, Zlatko
AU  - Suvajdžić Vuković, Nada
AU  - Pavlović, Sonja
AU  - Gašić, Vladimir
PY  - 2023
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/2127
AB  - Introduction: Acute myeloid leukemia (AML) is a heterogeneous malignant disease, that accounts for
80% of all acute leukemias in adults. Imprecise risk stratification and lack of personalized treatment creates a constant need to find new prognostic markers and targets for innovative therapeutics. Recently,
thissearch has pointed towards non-coding RNAs(ncRNA). Numerousstudies have shown dysregulation
of lncRNA GAS5 in cancers, but it was poorly investigated in AML. Since GAS5 actslike a molecularsponge
for miR-222, co-expression profiles of these non-coding RNAs could be novel prognostic markersin AML.
Methods: GAS5 expression levels were analysed in 94 AML patients and 14 healthy controls using RealTime PCR and miR-222 expression levels were analysed in a subgroup of 39 patients with normal karyotype (AML-NK). ROC curve analyses were used to find a cut-off value between GAS5high and GAS5low,
while the median value was used for distinguishing between miR-222high and miR-222low.
Results: We showed that GAS5 expression in AML patients was lower compared to healthy controls.
Lower GAS5 expression on diagnosis was related to an adverse prognosis. The disease-free survival and
the overallsurvival were lower in the GAS5low group butsurvival analysisfailed to confirm thisfinding. In
the AML-NK group patients had higher expression of miR-222 compared to healthy controls. A synergistic
effect of GAS5low/miR-222high status on disease prognosis was not established.
Conclusion:Our findingsindicate the potential prognostic significance of GAS5 expression and the need
for further investigation of these two non-coding RNAs and their potential roles in leukemogenesis.
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  - Expression profiles of long non-coding RNA gas5 and microrna-222 in younger AML patients
EP  - 72
SP  - 72
UR  - https://hdl.handle.net/21.15107/rcub_imagine_2127
ER  - 
@conference{
author = "Đorđe, Pavlović and Tošić, Nataša and Zukić, Branka and Pravić, Zlatko and Suvajdžić Vuković, Nada and Pavlović, Sonja and Gašić, Vladimir",
year = "2023",
abstract = "Introduction: Acute myeloid leukemia (AML) is a heterogeneous malignant disease, that accounts for
80% of all acute leukemias in adults. Imprecise risk stratification and lack of personalized treatment creates a constant need to find new prognostic markers and targets for innovative therapeutics. Recently,
thissearch has pointed towards non-coding RNAs(ncRNA). Numerousstudies have shown dysregulation
of lncRNA GAS5 in cancers, but it was poorly investigated in AML. Since GAS5 actslike a molecularsponge
for miR-222, co-expression profiles of these non-coding RNAs could be novel prognostic markersin AML.
Methods: GAS5 expression levels were analysed in 94 AML patients and 14 healthy controls using RealTime PCR and miR-222 expression levels were analysed in a subgroup of 39 patients with normal karyotype (AML-NK). ROC curve analyses were used to find a cut-off value between GAS5high and GAS5low,
while the median value was used for distinguishing between miR-222high and miR-222low.
Results: We showed that GAS5 expression in AML patients was lower compared to healthy controls.
Lower GAS5 expression on diagnosis was related to an adverse prognosis. The disease-free survival and
the overallsurvival were lower in the GAS5low group butsurvival analysisfailed to confirm thisfinding. In
the AML-NK group patients had higher expression of miR-222 compared to healthy controls. A synergistic
effect of GAS5low/miR-222high status on disease prognosis was not established.
Conclusion:Our findingsindicate the potential prognostic significance of GAS5 expression and the need
for further investigation of these two non-coding RNAs and their potential roles in leukemogenesis.",
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 = "Expression profiles of long non-coding RNA gas5 and microrna-222 in younger AML patients",
pages = "72-72",
url = "https://hdl.handle.net/21.15107/rcub_imagine_2127"
}
Đorđe, P., Tošić, N., Zukić, B., Pravić, Z., Suvajdžić Vuković, N., Pavlović, S.,& Gašić, V.. (2023). Expression profiles of long non-coding RNA gas5 and microrna-222 in younger AML patients. 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., 72-72.
https://hdl.handle.net/21.15107/rcub_imagine_2127
Đorđe P, Tošić N, Zukić B, Pravić Z, Suvajdžić Vuković N, Pavlović S, Gašić V. Expression profiles of long non-coding RNA gas5 and microrna-222 in younger AML patients. 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;:72-72.
https://hdl.handle.net/21.15107/rcub_imagine_2127 .
Đorđe, Pavlović, Tošić, Nataša, Zukić, Branka, Pravić, Zlatko, Suvajdžić Vuković, Nada, Pavlović, Sonja, Gašić, Vladimir, "Expression profiles of long non-coding RNA gas5 and microrna-222 in younger AML patients" 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):72-72,
https://hdl.handle.net/21.15107/rcub_imagine_2127 .

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 .

Rare case of myelodysplastic syndrome with near-tetraploidy and TP53 mutation

Čolović, Nataša; Đorđević, Vesna; Radojković, Milica; Karan-Đurašević, Teodora; Tošić, Nataša

(2023)

TY  - JOUR
AU  - Čolović, Nataša
AU  - Đorđević, Vesna
AU  - Radojković, Milica
AU  - Karan-Đurašević, Teodora
AU  - Tošić, Nataša
PY  - 2023
UR  - https://doiserbia.nb.rs/Article.aspx?ID=0370-81792300100C
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/2292
AB  - Introduction. Chromosomal numerical aberrations are very common in hematological malignancies, but near-tetraploidy (80-104 chromosomes) is rare in myeloid lineage malignancies, with only a few cases reported in myelodysplastic syndrome (MDS). Due to a small number of cases with this rare cytogenetic abnormality, clinicopathological significance of near-tetraploidy in MDS is still unknown. In this case report we present a case of de novo MDS patient with near-tetraploidy in association with TP53 mutation, and we aimed to elucidate the prognostic significance of this rare genetic feature. Case Outline. In August of 2018 a 71-year-old male presented with severe anemia, thrombocytopenia, and leucopenia and enlarged spleen. Laboratory data were as follows: hemoglobin (Hb) 93 g/L, white blood cells (WBC) 2.8×109/L and platelets 23x109/L. The bone marrow aspirate was hypercellular, megakaryocytes were not found, granulocytic cells were 15% with signs of dysplasia, with 16% of blast cells without Auer rods. The finding was in correlation with diagnosis of MDS, type RAEB2 which was also confirmed by immunophenotyping. Cytogenetic finding was near-tetraploidy (48,XY+mar[10]/92,XXYY[10]), and TP53 mutational analysis showed the presence of mutation in exon 8 (p.D281A; c.842 A>C). The patient received from time-to-time packed red blood cells and platelets, and died four months after initial diagnosis. Conclusion. Near-tetraploidy associated with TP53 mutation has been described only in few MDS cases. Results of these reports including ours suggest that the association of TP53 mutation and near-tetra polyploidy is a poor prognostic factor.
AB  - Нумеричке аберације хромозома су веома честе код хематолошких малигнитета, али су приближне тетраплои- дије (80–104 хромозома) ретке у малигнитетима мијелоидне лозе, са само неколико случајева пријављених у мијелоди- спластичком синдрому (МДС). Због малог броја случајева са овом ретком цитогенетском абнормалношћу, клиничко- -патолошки значај приближне тетраплоидије у МДС-у је још увек непознат. Овим приказом de novo болесника са МДС-ом, са приближном тетраплоидијом и мутацијом у гену TP53, циљ нам је био да расветлимо прогностички значај ове рет- ке генетске карактеристикe. Приказ болесника Приказан је 71-годишњи болесник који је у августу 2018. године развио симптоме тешке анемије, тромбоцитопеније, леукопеније и увећане слезине. Лабо- раторијске анализе су показале следеће: хемоглобин 93 g/L, леукоцити 2,8 × 109 /L и тромбоцити 23 × 109 /L. Аспират коштане сржи је био хиперћелијски, мегакариоцити нису на- ђени, 15% гранулоцитa је било са знацима дисплазије, 16% бластa без Ауерових штапића. Налаз је одговарао дијагнози МДС-а, типа рефракторне анемије са вишком бласта 2, што је потврђено и имунолошком фенотипизацијом. Цитогенет- ском анализом утврђено је присуство приближне тетрапло- идије (48,XY+mar10/92,XXYY[10]), а анализа мутација у гену TP53 показала је присуство мутације у егзону 8 (p.D281A; c.842 A > C). Болесник је по потреби примао трансфузију еритроцита и тромбоците, а умро је четири месеца након почетне дијагнозе. Закључак Присуство приближне тетраплоидије удружене са мутацијама у гену TP53 описано је само у неколико слу- чајева МДС-а. Резултати ових случајева, као и наши резул- тати, указују на то да приближна тетраплоидија повезана са присуством мутација у гену TP53 представља фактор лоше прогнозе.
T2  - Srpski arhiv za celokupno lekarstvo
T1  - Rare case of myelodysplastic syndrome with near-tetraploidy and TP53 mutation
T1  - Мијелодиспластични синдром са приближном тетраплоидијом удруженом са мутацијом гена TP53 – редак случај
EP  - n/a
IS  - n/a
SP  - n/a
DO  - 10.2298/SARH230728100C
ER  - 
@article{
author = "Čolović, Nataša and Đorđević, Vesna and Radojković, Milica and Karan-Đurašević, Teodora and Tošić, Nataša",
year = "2023",
abstract = "Introduction. Chromosomal numerical aberrations are very common in hematological malignancies, but near-tetraploidy (80-104 chromosomes) is rare in myeloid lineage malignancies, with only a few cases reported in myelodysplastic syndrome (MDS). Due to a small number of cases with this rare cytogenetic abnormality, clinicopathological significance of near-tetraploidy in MDS is still unknown. In this case report we present a case of de novo MDS patient with near-tetraploidy in association with TP53 mutation, and we aimed to elucidate the prognostic significance of this rare genetic feature. Case Outline. In August of 2018 a 71-year-old male presented with severe anemia, thrombocytopenia, and leucopenia and enlarged spleen. Laboratory data were as follows: hemoglobin (Hb) 93 g/L, white blood cells (WBC) 2.8×109/L and platelets 23x109/L. The bone marrow aspirate was hypercellular, megakaryocytes were not found, granulocytic cells were 15% with signs of dysplasia, with 16% of blast cells without Auer rods. The finding was in correlation with diagnosis of MDS, type RAEB2 which was also confirmed by immunophenotyping. Cytogenetic finding was near-tetraploidy (48,XY+mar[10]/92,XXYY[10]), and TP53 mutational analysis showed the presence of mutation in exon 8 (p.D281A; c.842 A>C). The patient received from time-to-time packed red blood cells and platelets, and died four months after initial diagnosis. Conclusion. Near-tetraploidy associated with TP53 mutation has been described only in few MDS cases. Results of these reports including ours suggest that the association of TP53 mutation and near-tetra polyploidy is a poor prognostic factor., Нумеричке аберације хромозома су веома честе код хематолошких малигнитета, али су приближне тетраплои- дије (80–104 хромозома) ретке у малигнитетима мијелоидне лозе, са само неколико случајева пријављених у мијелоди- спластичком синдрому (МДС). Због малог броја случајева са овом ретком цитогенетском абнормалношћу, клиничко- -патолошки значај приближне тетраплоидије у МДС-у је још увек непознат. Овим приказом de novo болесника са МДС-ом, са приближном тетраплоидијом и мутацијом у гену TP53, циљ нам је био да расветлимо прогностички значај ове рет- ке генетске карактеристикe. Приказ болесника Приказан је 71-годишњи болесник који је у августу 2018. године развио симптоме тешке анемије, тромбоцитопеније, леукопеније и увећане слезине. Лабо- раторијске анализе су показале следеће: хемоглобин 93 g/L, леукоцити 2,8 × 109 /L и тромбоцити 23 × 109 /L. Аспират коштане сржи је био хиперћелијски, мегакариоцити нису на- ђени, 15% гранулоцитa је било са знацима дисплазије, 16% бластa без Ауерових штапића. Налаз је одговарао дијагнози МДС-а, типа рефракторне анемије са вишком бласта 2, што је потврђено и имунолошком фенотипизацијом. Цитогенет- ском анализом утврђено је присуство приближне тетрапло- идије (48,XY+mar10/92,XXYY[10]), а анализа мутација у гену TP53 показала је присуство мутације у егзону 8 (p.D281A; c.842 A > C). Болесник је по потреби примао трансфузију еритроцита и тромбоците, а умро је четири месеца након почетне дијагнозе. Закључак Присуство приближне тетраплоидије удружене са мутацијама у гену TP53 описано је само у неколико слу- чајева МДС-а. Резултати ових случајева, као и наши резул- тати, указују на то да приближна тетраплоидија повезана са присуством мутација у гену TP53 представља фактор лоше прогнозе.",
journal = "Srpski arhiv za celokupno lekarstvo",
title = "Rare case of myelodysplastic syndrome with near-tetraploidy and TP53 mutation, Мијелодиспластични синдром са приближном тетраплоидијом удруженом са мутацијом гена TP53 – редак случај",
pages = "n/a-n/a",
number = "n/a",
doi = "10.2298/SARH230728100C"
}
Čolović, N., Đorđević, V., Radojković, M., Karan-Đurašević, T.,& Tošić, N.. (2023). Rare case of myelodysplastic syndrome with near-tetraploidy and TP53 mutation. in Srpski arhiv za celokupno lekarstvo(n/a), n/a-n/a.
https://doi.org/10.2298/SARH230728100C
Čolović N, Đorđević V, Radojković M, Karan-Đurašević T, Tošić N. Rare case of myelodysplastic syndrome with near-tetraploidy and TP53 mutation. in Srpski arhiv za celokupno lekarstvo. 2023;(n/a):n/a-n/a.
doi:10.2298/SARH230728100C .
Čolović, Nataša, Đorđević, Vesna, Radojković, Milica, Karan-Đurašević, Teodora, Tošić, Nataša, "Rare case of myelodysplastic syndrome with near-tetraploidy and TP53 mutation" in Srpski arhiv za celokupno lekarstvo, no. n/a (2023):n/a-n/a,
https://doi.org/10.2298/SARH230728100C . .

The influence of BCL2, BAX, and ABCB1 gene expression on prognosis of adult de novo acute myeloid leukemia with normal karyotype patients

Pravdić, Zlatko; Vuković, Nada Suvajdžić; Gašić, Vladimir; Marjanović, Irena; Karan-Đurašević, Teodora; Pavlović, Sonja; Tošić, Nataša

(Sciendo, 2023)

TY  - JOUR
AU  - Pravdić, Zlatko
AU  - Vuković, Nada Suvajdžić
AU  - Gašić, Vladimir
AU  - Marjanović, Irena
AU  - Karan-Đurašević, Teodora
AU  - Pavlović, Sonja
AU  - Tošić, Nataša
PY  - 2023
UR  - https://sciendo.com/article/10.2478/raon-2023-0017
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/2291
AB  - Background: Deregulation of the apoptotic process underlies the pathogenesis of many cancers, including leukemia, but is also very important for the success of chemotherapy treatment. Therefore, the gene expression profile of main apoptotic factors, such as anti-apoptotic BCL2 (B-cell lymphoma protein 2) and pro-apoptotic BAX (BCL2-associated X), as well as genes involved in the multi-drug resistance (ABCB1), could have significant impact on the prognosis and could be used as targets for specific therapy.Patients and methodsWe analyzed the expression of BCL2, BAX, and ABCB1 in bone-marrow samples collected at diagnosis from 51 adult patients with acute myeloid leukemia with normal karyotype (AML-NK) using real-time polymerase chain reaction method, and examined their prognostic potential.ResultsIncreased expression of BCL2 (BCL2+) was associated with the presence of chemoresistance (p = 0.024), while patients with low BAX expression were more prone to relapse (p = 0.047). Analysis of the combined effect of BCL2 and BAX expression showed that 87% of patients with BAX/BCL2low status were resistant to therapy (p = 0.044). High expression of ABCB1 was associated with BCL2+ status (p &lt; 0.001), and with absence FLT3-ITD mutations (p = 0.019).ConclusionsThe present analysis of BCL2, BAX, and ABCB1 gene expression profiles is the first study focusing solely
PB  - Sciendo
T2  - Radiology and Oncology
T1  - The influence of BCL2, BAX, and ABCB1 gene expression on prognosis of adult de novo acute myeloid leukemia with normal karyotype patients
EP  - 248
IS  - 2
SP  - 239
VL  - 57
DO  - 10.2478/raon-2023-0017
ER  - 
@article{
author = "Pravdić, Zlatko and Vuković, Nada Suvajdžić and Gašić, Vladimir and Marjanović, Irena and Karan-Đurašević, Teodora and Pavlović, Sonja and Tošić, Nataša",
year = "2023",
abstract = "Background: Deregulation of the apoptotic process underlies the pathogenesis of many cancers, including leukemia, but is also very important for the success of chemotherapy treatment. Therefore, the gene expression profile of main apoptotic factors, such as anti-apoptotic BCL2 (B-cell lymphoma protein 2) and pro-apoptotic BAX (BCL2-associated X), as well as genes involved in the multi-drug resistance (ABCB1), could have significant impact on the prognosis and could be used as targets for specific therapy.Patients and methodsWe analyzed the expression of BCL2, BAX, and ABCB1 in bone-marrow samples collected at diagnosis from 51 adult patients with acute myeloid leukemia with normal karyotype (AML-NK) using real-time polymerase chain reaction method, and examined their prognostic potential.ResultsIncreased expression of BCL2 (BCL2+) was associated with the presence of chemoresistance (p = 0.024), while patients with low BAX expression were more prone to relapse (p = 0.047). Analysis of the combined effect of BCL2 and BAX expression showed that 87% of patients with BAX/BCL2low status were resistant to therapy (p = 0.044). High expression of ABCB1 was associated with BCL2+ status (p &lt; 0.001), and with absence FLT3-ITD mutations (p = 0.019).ConclusionsThe present analysis of BCL2, BAX, and ABCB1 gene expression profiles is the first study focusing solely",
publisher = "Sciendo",
journal = "Radiology and Oncology",
title = "The influence of BCL2, BAX, and ABCB1 gene expression on prognosis of adult de novo acute myeloid leukemia with normal karyotype patients",
pages = "248-239",
number = "2",
volume = "57",
doi = "10.2478/raon-2023-0017"
}
Pravdić, Z., Vuković, N. S., Gašić, V., Marjanović, I., Karan-Đurašević, T., Pavlović, S.,& Tošić, N.. (2023). The influence of BCL2, BAX, and ABCB1 gene expression on prognosis of adult de novo acute myeloid leukemia with normal karyotype patients. in Radiology and Oncology
Sciendo., 57(2), 239-248.
https://doi.org/10.2478/raon-2023-0017
Pravdić Z, Vuković NS, Gašić V, Marjanović I, Karan-Đurašević T, Pavlović S, Tošić N. The influence of BCL2, BAX, and ABCB1 gene expression on prognosis of adult de novo acute myeloid leukemia with normal karyotype patients. in Radiology and Oncology. 2023;57(2):239-248.
doi:10.2478/raon-2023-0017 .
Pravdić, Zlatko, Vuković, Nada Suvajdžić, Gašić, Vladimir, Marjanović, Irena, Karan-Đurašević, Teodora, Pavlović, Sonja, Tošić, Nataša, "The influence of BCL2, BAX, and ABCB1 gene expression on prognosis of adult de novo acute myeloid leukemia with normal karyotype patients" in Radiology and Oncology, 57, no. 2 (2023):239-248,
https://doi.org/10.2478/raon-2023-0017 . .
2
1

Pediatric acute myeloid leukemia: Insight into genetic landscape and novel targeted approaches

Tošic, Natasa; Marjanović, Irena; Lazić, Jelena

(2023)

TY  - JOUR
AU  - Tošic, Natasa
AU  - Marjanović, Irena
AU  - Lazić, Jelena
PY  - 2023
UR  - https://www.sciencedirect.com/science/article/pii/S0006295223002964
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/2103
AB  - Acute myeloid leukemia (AML) is a very heterogeneous hematological malignancy that accounts for approximately 20% of all pediatric leukemia cases. The outcome of pediatric AML has improved over the last decades, with overall survival rates reaching up to 70%. Still, AML is among the leading types of pediatric cancers by its high mortality rate. Modulation of standard therapy, like chemotherapy intensification, hematopoietic stem cell transplantation and optimized supportive care, could only get this far, but for the significant improvement of the outcome in pediatric AML, development of novel targeted therapy approaches is necessary. In recent years the advances in genomic techniques have greatly expanded our knowledge of the AML biology, revealing molecular landscape and complexity of the disease, which in turn have led to the identification of novel therapeutic targets. This review provides a brief overview of the genetic landscape of pediatric AML, and how it’s used for precise molecular characterization and risk stratification of the patients, and also for the development of effective targeted therapy. Furthermore, this review presents recent advances in molecular targeted therapy and immunotherapy with an emphasis on the therapeutic approaches with significant clinical benefits for pediatric AML.
T2  - Biochemical Pharmacology
T1  - Pediatric acute myeloid leukemia: Insight into genetic landscape and novel targeted approaches
SP  - 115705
VL  - 215
DO  - 10.1016/j.bcp.2023.115705
ER  - 
@article{
author = "Tošic, Natasa and Marjanović, Irena and Lazić, Jelena",
year = "2023",
abstract = "Acute myeloid leukemia (AML) is a very heterogeneous hematological malignancy that accounts for approximately 20% of all pediatric leukemia cases. The outcome of pediatric AML has improved over the last decades, with overall survival rates reaching up to 70%. Still, AML is among the leading types of pediatric cancers by its high mortality rate. Modulation of standard therapy, like chemotherapy intensification, hematopoietic stem cell transplantation and optimized supportive care, could only get this far, but for the significant improvement of the outcome in pediatric AML, development of novel targeted therapy approaches is necessary. In recent years the advances in genomic techniques have greatly expanded our knowledge of the AML biology, revealing molecular landscape and complexity of the disease, which in turn have led to the identification of novel therapeutic targets. This review provides a brief overview of the genetic landscape of pediatric AML, and how it’s used for precise molecular characterization and risk stratification of the patients, and also for the development of effective targeted therapy. Furthermore, this review presents recent advances in molecular targeted therapy and immunotherapy with an emphasis on the therapeutic approaches with significant clinical benefits for pediatric AML.",
journal = "Biochemical Pharmacology",
title = "Pediatric acute myeloid leukemia: Insight into genetic landscape and novel targeted approaches",
pages = "115705",
volume = "215",
doi = "10.1016/j.bcp.2023.115705"
}
Tošic, N., Marjanović, I.,& Lazić, J.. (2023). Pediatric acute myeloid leukemia: Insight into genetic landscape and novel targeted approaches. in Biochemical Pharmacology, 215, 115705.
https://doi.org/10.1016/j.bcp.2023.115705
Tošic N, Marjanović I, Lazić J. Pediatric acute myeloid leukemia: Insight into genetic landscape and novel targeted approaches. in Biochemical Pharmacology. 2023;215:115705.
doi:10.1016/j.bcp.2023.115705 .
Tošic, Natasa, Marjanović, Irena, Lazić, Jelena, "Pediatric acute myeloid leukemia: Insight into genetic landscape and novel targeted approaches" in Biochemical Pharmacology, 215 (2023):115705,
https://doi.org/10.1016/j.bcp.2023.115705 . .
1
3
3

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 . .

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

Ekspresioni obrazac duge nekodirajuće RNK GAS5 i mikroRNK- 222 kod mlađih pacijenata obolelih od AML

Pavlović, Đorđe; Tošić, Nataša; Zukić, Branka; Pravdić, Zlatko; Suvajdžić Vuković, Nada; Pavlović, Sonja; Gašić, Vladimir

(Beograd : Srpsko biološko društvo, 2022)

TY  - CONF
AU  - Pavlović, Đorđe
AU  - Tošić, Nataša
AU  - Zukić, Branka
AU  - Pravdić, Zlatko
AU  - Suvajdžić Vuković, Nada
AU  - Pavlović, Sonja
AU  - Gašić, Vladimir
PY  - 2022
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/1742
AB  - Akutna mijeloidna leukemija (AML) je heterogeno maligno oboljenje kako na
kliničkom tako i na genetičkom nivou. AML ima lošu prognozu, i zato postoji
konstantna potreba za novim prognostičkim markerima, kao i markerima koji
mogu biti mete za inovativne terapeutike. U skorije vreme potraga za novim
biomarkerima je naučnicima skrenula pažnju ka nekodirajućim RNK, naročito
dugim nekodirajućim RNK (dnkRNK) i mikroRNK (miRNK). U ovom radu ispitali
smo nivo ekspresije „growth arrest-specific transcript 5“ (GAS5) dnkRNK kod 94
mlađih osoba obolelih od AML, kao i nivo ekspresije miR-222 u grupi od 39
osoba obolelih od AML sa normalnim kariotipom (AML-NK), u cilju da
ispitamo njihov prognostički potencijal. Naši rezultati su pokazali da je nivo
ekspresije GAS5 kod obolelih od AML niži u poređenju sa zdravim kontrolama, i
češći je u grupi sa nepovoljnom prognozom. U AML-NK grupi pacijenti su imali
povišenu ekspresiju miR-222 u poređenju sa zdravim kontrolama. Sinergistički
efekat „GAS5low/miR-222 high“ nije utvrđen. Ovo je prva studija koja je ispitala
interakciju ekspresije GAS5 i miR-222 kod obolelih od AML. Naši rezultati
indikuju potrebu za daljim ispitivanjem ove dve nekodirajuće RNK i njihove
potencijalne uloge u leukemogenezi i prognostici AML pacijenata.
AB  - Акутна мијелоидна леукемија (АМЛ) је хетерогено малигно обољење како на
клиничком тако и на генетичком нивоу. АМЛ има лошу прогнозу, и зато постоји
константна потреба за новим прогностичким маркерима, као и маркерима који
могу бити мете за иновативне терапеутике. У скорије време потрага за новим
биомаркерима је научницима скренула пажњу ка некодирајућим РНК, нарочито
дугим некодирајућим РНК (днкРНК) и микроРНК (миРНК). У овом раду испитали
смо ниво експресије „growth arrest-specific transcript 5“ (GAS5) днкРНК код 94
млађих особа оболелих од АМЛ, као и ниво експресије miR-222 у групи од 39
особа оболелих од АМЛ са нормалним кариотипом (АМЛ-НК), у циљу да
испитамо њихов прогностички потенцијал. Наши резултати су показали да је ниво
експресије GAS5 код оболелих од АМЛ нижи у поређењу са здравим контролама, и
чешћи је у групи са неповољном прогнозом. У АМЛ-НК групи пацијенти су имали
повишену експресију miR-222 у поређењу са здравим контролама. Синергистички
ефекат „GAS5low/miR-222 high“ није утврђен. Ово је прва студија која је испитала
интеракцију експресије GAS5 и miR-222 код оболелих од АМЛ. Наши резултати
индикују потребу за даљим испитивањем ове две некодирајуће РНК и њихове
потенцијалне улоге у леукемогенези и прогностици АМЛ пацијената.
PB  - Beograd : Srpsko biološko društvo
C3  - Treći kongres biologa Srbije
T1  - Ekspresioni obrazac duge nekodirajuće RNK GAS5 i mikroRNK- 222 kod mlađih pacijenata obolelih od AML
T1  - Експресиони образац дуге некодирајуће РНК GAS5 и микроРНК- 222 код млађих пацијената оболелих од АМЛ
SP  - 302
UR  - https://hdl.handle.net/21.15107/rcub_imagine_1742
ER  - 
@conference{
author = "Pavlović, Đorđe and Tošić, Nataša and Zukić, Branka and Pravdić, Zlatko and Suvajdžić Vuković, Nada and Pavlović, Sonja and Gašić, Vladimir",
year = "2022",
abstract = "Akutna mijeloidna leukemija (AML) je heterogeno maligno oboljenje kako na
kliničkom tako i na genetičkom nivou. AML ima lošu prognozu, i zato postoji
konstantna potreba za novim prognostičkim markerima, kao i markerima koji
mogu biti mete za inovativne terapeutike. U skorije vreme potraga za novim
biomarkerima je naučnicima skrenula pažnju ka nekodirajućim RNK, naročito
dugim nekodirajućim RNK (dnkRNK) i mikroRNK (miRNK). U ovom radu ispitali
smo nivo ekspresije „growth arrest-specific transcript 5“ (GAS5) dnkRNK kod 94
mlađih osoba obolelih od AML, kao i nivo ekspresije miR-222 u grupi od 39
osoba obolelih od AML sa normalnim kariotipom (AML-NK), u cilju da
ispitamo njihov prognostički potencijal. Naši rezultati su pokazali da je nivo
ekspresije GAS5 kod obolelih od AML niži u poređenju sa zdravim kontrolama, i
češći je u grupi sa nepovoljnom prognozom. U AML-NK grupi pacijenti su imali
povišenu ekspresiju miR-222 u poređenju sa zdravim kontrolama. Sinergistički
efekat „GAS5low/miR-222 high“ nije utvrđen. Ovo je prva studija koja je ispitala
interakciju ekspresije GAS5 i miR-222 kod obolelih od AML. Naši rezultati
indikuju potrebu za daljim ispitivanjem ove dve nekodirajuće RNK i njihove
potencijalne uloge u leukemogenezi i prognostici AML pacijenata., Акутна мијелоидна леукемија (АМЛ) је хетерогено малигно обољење како на
клиничком тако и на генетичком нивоу. АМЛ има лошу прогнозу, и зато постоји
константна потреба за новим прогностичким маркерима, као и маркерима који
могу бити мете за иновативне терапеутике. У скорије време потрага за новим
биомаркерима је научницима скренула пажњу ка некодирајућим РНК, нарочито
дугим некодирајућим РНК (днкРНК) и микроРНК (миРНК). У овом раду испитали
смо ниво експресије „growth arrest-specific transcript 5“ (GAS5) днкРНК код 94
млађих особа оболелих од АМЛ, као и ниво експресије miR-222 у групи од 39
особа оболелих од АМЛ са нормалним кариотипом (АМЛ-НК), у циљу да
испитамо њихов прогностички потенцијал. Наши резултати су показали да је ниво
експресије GAS5 код оболелих од АМЛ нижи у поређењу са здравим контролама, и
чешћи је у групи са неповољном прогнозом. У АМЛ-НК групи пацијенти су имали
повишену експресију miR-222 у поређењу са здравим контролама. Синергистички
ефекат „GAS5low/miR-222 high“ није утврђен. Ово је прва студија која је испитала
интеракцију експресије GAS5 и miR-222 код оболелих од АМЛ. Наши резултати
индикују потребу за даљим испитивањем ове две некодирајуће РНК и њихове
потенцијалне улоге у леукемогенези и прогностици АМЛ пацијената.",
publisher = "Beograd : Srpsko biološko društvo",
journal = "Treći kongres biologa Srbije",
title = "Ekspresioni obrazac duge nekodirajuće RNK GAS5 i mikroRNK- 222 kod mlađih pacijenata obolelih od AML, Експресиони образац дуге некодирајуће РНК GAS5 и микроРНК- 222 код млађих пацијената оболелих од АМЛ",
pages = "302",
url = "https://hdl.handle.net/21.15107/rcub_imagine_1742"
}
Pavlović, Đ., Tošić, N., Zukić, B., Pravdić, Z., Suvajdžić Vuković, N., Pavlović, S.,& Gašić, V.. (2022). Ekspresioni obrazac duge nekodirajuće RNK GAS5 i mikroRNK- 222 kod mlađih pacijenata obolelih od AML. in Treći kongres biologa Srbije
Beograd : Srpsko biološko društvo., 302.
https://hdl.handle.net/21.15107/rcub_imagine_1742
Pavlović Đ, Tošić N, Zukić B, Pravdić Z, Suvajdžić Vuković N, Pavlović S, Gašić V. Ekspresioni obrazac duge nekodirajuće RNK GAS5 i mikroRNK- 222 kod mlađih pacijenata obolelih od AML. in Treći kongres biologa Srbije. 2022;:302.
https://hdl.handle.net/21.15107/rcub_imagine_1742 .
Pavlović, Đorđe, Tošić, Nataša, Zukić, Branka, Pravdić, Zlatko, Suvajdžić Vuković, Nada, Pavlović, Sonja, Gašić, Vladimir, "Ekspresioni obrazac duge nekodirajuće RNK GAS5 i mikroRNK- 222 kod mlađih pacijenata obolelih od AML" in Treći kongres biologa Srbije (2022):302,
https://hdl.handle.net/21.15107/rcub_imagine_1742 .

Molekularna dijagnostika Fabrijeve bolesti kod pacijenata sa hroničnom bubrežnom insuficijencijom nepoznate etiologije

Parezanović, Marina; Stojiljković, Maja; Anđelković, Marina; Stevanović, Nina; Spasovski, Vesna; Ugrin, Milena; Komazec, Jovana; Tošić, Nataša; Pavlović, Sonja; Ćelić, Dejan; Vučenović, Jelica; Skakić, Anita

(Beograd : Srpsko biološko društvo, 2022)

TY  - CONF
AU  - Parezanović, Marina
AU  - Stojiljković, Maja
AU  - Anđelković, Marina
AU  - Stevanović, Nina
AU  - Spasovski, Vesna
AU  - Ugrin, Milena
AU  - Komazec, Jovana
AU  - Tošić, Nataša
AU  - Pavlović, Sonja
AU  - Ćelić, Dejan
AU  - Vučenović, Jelica
AU  - Skakić, Anita
PY  - 2022
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/1740
AB  - Fabrijeva bolest (FB) je retka, monogenska bolest, koja se odlikuje veoma
heterogenom kliničkom slikom izazvanom promenama u genu GLA, smeštenom na
dugom kraku hromozoma H. Usled narušene funkcije lizozomalnog enzima α-
galaktozidaze A dolazi do nagomilavanja Gb3 supstrata, što dovodi do
multisistemskih oštećenja. Precizna molekularno-genetička dijagnoza je
esencijalna kako bi se pacijentima omogućilo pravovremeno lečenje. U našoj
studiji, analizirano je 95 ispitanika suspektnih na FB Sangerovim
sekvenciranjem svih egzona i okolnih intronskih regiona gena GLA, nakon čega je
izmerena relativna ekspresija kod 6 pacijenata. Genetičkom analizom kod 3
pacijenta detektovana je kodirajuća varijanta (p.D313Y), dok je kod 10 pacijenata
detektovana kombinacija intronskih varijanti, opisanih kao kompleksni
intronski haplotip (KIH). KIH1 (c.-10C>T, c.370-81_370-77delCAGCC, c.640-
16A>G, c.1000-22C>T), najčešći haplotip, detektovan je kod 7 (7,4%) pacijenata.
Uprkos normalnim biohemijskim parametrima, rezultati RT-qPCR metode
pokazali su snižen nivo ekspresije gena GLA u perifernoj krvi za 9,1%, 7,4%,
46,3% kod dve pacijentkinje (KIH1) i jedne pacijentkinje kod koje je detektovana
promotorska varijanta c.-10C>T, respektivno, ukazujući na potrebu dodatnih
analiza za konačno uspostavljanje dijagnoze FB. Uzevši u obzir da efekat
intronskih haplotipova nije funkcionalno okarakterisan, naša studija ukazuje
na važnost analiziranja intronskih regiona gena GLA kao potencijalnih
genetičkih modifikatora FB.
AB  - Фабријева болест (ФБ) је ретка, моногенска болест, која се одликује веома
хетерогеном клиничком сликом изазваном променама у гену GLA, смештеном на
дугом краку хромозома Х. Услед нарушене функције лизозомалног ензима α-
галактозидазе А долази до нагомилавања Gb3 супстрата, што доводи до
мултисистемских оштећења. Прецизна молекуларно-генетичка дијагноза је
есенцијална како би се пацијентима омогућило правовремено лечење. У нашој
студији, анализирано је 95 испитаника суспектних на ФБ Сангеровим
секвенцирањем свих егзона и околних интронских региона гена GLA, након чега је
измерена релативна експресија код 6 пацијената. Генетичком анализом код 3
пацијента детектована је кодирајућа варијанта (p.D313Y), док је код 10 пацијената
детектована комбинација интронских варијанти, описаних као комплексни
интронски хаплотип (КИХ). КИХ1 (c.-10C>T, c.370-81_370-77delCAGCC, c.640-
16A>G, c.1000-22C>T), најчешћи хаплотип, детектован је код 7 (7,4%) пацијената.
Упркос нормалним биохемијским параметрима, резултати RT-qPCR методе
показали су снижен ниво експресије гена GLA у периферној крви за 9,1%, 7,4%,
46,3% код две пацијенткиње (КИХ1) и једне пацијенткиње код које је детектована
промоторска варијанта c.-10C>T, респективно, указујући на потребу додатних
анализа за коначно успостављање дијагнозе ФБ. Узевши у обзир да ефекат
интронских хаплотипова није функционално окарактерисан, наша студија указује
на важност анализирања интронских региона гена GLA као потенцијалних
генетичких модификатора ФБ.
PB  - Beograd : Srpsko biološko društvo
C3  - Treći kongres biologa Srbije
T1  - Molekularna dijagnostika Fabrijeve bolesti kod pacijenata sa hroničnom bubrežnom insuficijencijom nepoznate etiologije
T1  - Молекуларна дијагностика Фабријеве болести код пацијената са хроничном бубрежном инсуфицијенцијом непознате етиологије
SP  - 313
UR  - https://hdl.handle.net/21.15107/rcub_imagine_1740
ER  - 
@conference{
author = "Parezanović, Marina and Stojiljković, Maja and Anđelković, Marina and Stevanović, Nina and Spasovski, Vesna and Ugrin, Milena and Komazec, Jovana and Tošić, Nataša and Pavlović, Sonja and Ćelić, Dejan and Vučenović, Jelica and Skakić, Anita",
year = "2022",
abstract = "Fabrijeva bolest (FB) je retka, monogenska bolest, koja se odlikuje veoma
heterogenom kliničkom slikom izazvanom promenama u genu GLA, smeštenom na
dugom kraku hromozoma H. Usled narušene funkcije lizozomalnog enzima α-
galaktozidaze A dolazi do nagomilavanja Gb3 supstrata, što dovodi do
multisistemskih oštećenja. Precizna molekularno-genetička dijagnoza je
esencijalna kako bi se pacijentima omogućilo pravovremeno lečenje. U našoj
studiji, analizirano je 95 ispitanika suspektnih na FB Sangerovim
sekvenciranjem svih egzona i okolnih intronskih regiona gena GLA, nakon čega je
izmerena relativna ekspresija kod 6 pacijenata. Genetičkom analizom kod 3
pacijenta detektovana je kodirajuća varijanta (p.D313Y), dok je kod 10 pacijenata
detektovana kombinacija intronskih varijanti, opisanih kao kompleksni
intronski haplotip (KIH). KIH1 (c.-10C>T, c.370-81_370-77delCAGCC, c.640-
16A>G, c.1000-22C>T), najčešći haplotip, detektovan je kod 7 (7,4%) pacijenata.
Uprkos normalnim biohemijskim parametrima, rezultati RT-qPCR metode
pokazali su snižen nivo ekspresije gena GLA u perifernoj krvi za 9,1%, 7,4%,
46,3% kod dve pacijentkinje (KIH1) i jedne pacijentkinje kod koje je detektovana
promotorska varijanta c.-10C>T, respektivno, ukazujući na potrebu dodatnih
analiza za konačno uspostavljanje dijagnoze FB. Uzevši u obzir da efekat
intronskih haplotipova nije funkcionalno okarakterisan, naša studija ukazuje
na važnost analiziranja intronskih regiona gena GLA kao potencijalnih
genetičkih modifikatora FB., Фабријева болест (ФБ) је ретка, моногенска болест, која се одликује веома
хетерогеном клиничком сликом изазваном променама у гену GLA, смештеном на
дугом краку хромозома Х. Услед нарушене функције лизозомалног ензима α-
галактозидазе А долази до нагомилавања Gb3 супстрата, што доводи до
мултисистемских оштећења. Прецизна молекуларно-генетичка дијагноза је
есенцијална како би се пацијентима омогућило правовремено лечење. У нашој
студији, анализирано је 95 испитаника суспектних на ФБ Сангеровим
секвенцирањем свих егзона и околних интронских региона гена GLA, након чега је
измерена релативна експресија код 6 пацијената. Генетичком анализом код 3
пацијента детектована је кодирајућа варијанта (p.D313Y), док је код 10 пацијената
детектована комбинација интронских варијанти, описаних као комплексни
интронски хаплотип (КИХ). КИХ1 (c.-10C>T, c.370-81_370-77delCAGCC, c.640-
16A>G, c.1000-22C>T), најчешћи хаплотип, детектован је код 7 (7,4%) пацијената.
Упркос нормалним биохемијским параметрима, резултати RT-qPCR методе
показали су снижен ниво експресије гена GLA у периферној крви за 9,1%, 7,4%,
46,3% код две пацијенткиње (КИХ1) и једне пацијенткиње код које је детектована
промоторска варијанта c.-10C>T, респективно, указујући на потребу додатних
анализа за коначно успостављање дијагнозе ФБ. Узевши у обзир да ефекат
интронских хаплотипова није функционално окарактерисан, наша студија указује
на важност анализирања интронских региона гена GLA као потенцијалних
генетичких модификатора ФБ.",
publisher = "Beograd : Srpsko biološko društvo",
journal = "Treći kongres biologa Srbije",
title = "Molekularna dijagnostika Fabrijeve bolesti kod pacijenata sa hroničnom bubrežnom insuficijencijom nepoznate etiologije, Молекуларна дијагностика Фабријеве болести код пацијената са хроничном бубрежном инсуфицијенцијом непознате етиологије",
pages = "313",
url = "https://hdl.handle.net/21.15107/rcub_imagine_1740"
}
Parezanović, M., Stojiljković, M., Anđelković, M., Stevanović, N., Spasovski, V., Ugrin, M., Komazec, J., Tošić, N., Pavlović, S., Ćelić, D., Vučenović, J.,& Skakić, A.. (2022). Molekularna dijagnostika Fabrijeve bolesti kod pacijenata sa hroničnom bubrežnom insuficijencijom nepoznate etiologije. in Treći kongres biologa Srbije
Beograd : Srpsko biološko društvo., 313.
https://hdl.handle.net/21.15107/rcub_imagine_1740
Parezanović M, Stojiljković M, Anđelković M, Stevanović N, Spasovski V, Ugrin M, Komazec J, Tošić N, Pavlović S, Ćelić D, Vučenović J, Skakić A. Molekularna dijagnostika Fabrijeve bolesti kod pacijenata sa hroničnom bubrežnom insuficijencijom nepoznate etiologije. in Treći kongres biologa Srbije. 2022;:313.
https://hdl.handle.net/21.15107/rcub_imagine_1740 .
Parezanović, Marina, Stojiljković, Maja, Anđelković, Marina, Stevanović, Nina, Spasovski, Vesna, Ugrin, Milena, Komazec, Jovana, Tošić, Nataša, Pavlović, Sonja, Ćelić, Dejan, Vučenović, Jelica, Skakić, Anita, "Molekularna dijagnostika Fabrijeve bolesti kod pacijenata sa hroničnom bubrežnom insuficijencijom nepoznate etiologije" in Treći kongres biologa Srbije (2022):313,
https://hdl.handle.net/21.15107/rcub_imagine_1740 .

Diagnostic and Therapeutic Implications of Long Non-Coding RNAs in Leukemia

Gašić, Vladimir; Karan-Đurašević, Teodora; Pavlović, Đorđe; Zukić, Branka; Pavlović, Sonja; Tošić, Nataša

(2022)

TY  - JOUR
AU  - Gašić, Vladimir
AU  - Karan-Đurašević, Teodora
AU  - Pavlović, Đorđe
AU  - Zukić, Branka
AU  - Pavlović, Sonja
AU  - Tošić, Nataša
PY  - 2022
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/1660
AB  - Leukemia is a heterogenous group of hematological malignancies categorized in four main types (acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL), chronic myeloid leukemia (CML) and chronic lymphocytic leukemia (CLL). Several cytogenetic and molecular markers have become a part of routine analysis for leukemia patients. These markers have been used in diagnosis, risk-stratification and targeted therapy application. Recent studies have indicated that numerous regulatory RNAs, such as long non-coding RNAs (lncRNAs), have a role in tumor initiation and progression. When it comes to leukemia, data for lncRNA involvement in its etiology, progression, diagnosis, treatment and prognosis is limited. The aim of this review is to summarize research data on lncRNAs in different types of leukemia, on their expression pattern, their role in leukemic transformation and disease progression. The usefulness of this information in the clinical setting, i.e., for diagnostic and prognostic purposes, will be emphasized. Finally, how particular lncRNAs could be used as potential targets for the application of targeted therapy will be considered.
T2  - Life
T2  - Life
T1  - Diagnostic and Therapeutic Implications of Long Non-Coding RNAs in Leukemia
IS  - 11
SP  - 1770
VL  - 12
DO  - 10.3390/life12111770
ER  - 
@article{
author = "Gašić, Vladimir and Karan-Đurašević, Teodora and Pavlović, Đorđe and Zukić, Branka and Pavlović, Sonja and Tošić, Nataša",
year = "2022",
abstract = "Leukemia is a heterogenous group of hematological malignancies categorized in four main types (acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL), chronic myeloid leukemia (CML) and chronic lymphocytic leukemia (CLL). Several cytogenetic and molecular markers have become a part of routine analysis for leukemia patients. These markers have been used in diagnosis, risk-stratification and targeted therapy application. Recent studies have indicated that numerous regulatory RNAs, such as long non-coding RNAs (lncRNAs), have a role in tumor initiation and progression. When it comes to leukemia, data for lncRNA involvement in its etiology, progression, diagnosis, treatment and prognosis is limited. The aim of this review is to summarize research data on lncRNAs in different types of leukemia, on their expression pattern, their role in leukemic transformation and disease progression. The usefulness of this information in the clinical setting, i.e., for diagnostic and prognostic purposes, will be emphasized. Finally, how particular lncRNAs could be used as potential targets for the application of targeted therapy will be considered.",
journal = "Life, Life",
title = "Diagnostic and Therapeutic Implications of Long Non-Coding RNAs in Leukemia",
number = "11",
pages = "1770",
volume = "12",
doi = "10.3390/life12111770"
}
Gašić, V., Karan-Đurašević, T., Pavlović, Đ., Zukić, B., Pavlović, S.,& Tošić, N.. (2022). Diagnostic and Therapeutic Implications of Long Non-Coding RNAs in Leukemia. in Life, 12(11), 1770.
https://doi.org/10.3390/life12111770
Gašić V, Karan-Đurašević T, Pavlović Đ, Zukić B, Pavlović S, Tošić N. Diagnostic and Therapeutic Implications of Long Non-Coding RNAs in Leukemia. in Life. 2022;12(11):1770.
doi:10.3390/life12111770 .
Gašić, Vladimir, Karan-Đurašević, Teodora, Pavlović, Đorđe, Zukić, Branka, Pavlović, Sonja, Tošić, Nataša, "Diagnostic and Therapeutic Implications of Long Non-Coding RNAs in Leukemia" in Life, 12, no. 11 (2022):1770,
https://doi.org/10.3390/life12111770 . .
1
10
8

Expression Profiles of Long Non-Coding RNA GAS5 and MicroRNA-222 in Younger AML Patients

Pavlović, Đorđe; Tošić, Nataša; Zukić, Branka; Pravdić, Zlatko; Suvajdžić-Vuković, Nada; Pavlović, Sonja; Gašić, Vladimir

(MDPI, Basel, 2022)

TY  - JOUR
AU  - Pavlović, Đorđe
AU  - Tošić, Nataša
AU  - Zukić, Branka
AU  - Pravdić, Zlatko
AU  - Suvajdžić-Vuković, Nada
AU  - Pavlović, Sonja
AU  - Gašić, Vladimir
PY  - 2022
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/1573
AB  - Acute myeloid leukemia (AML) is a heterogeneous malignant disease both on clinical and genetic levels. AML has poor prognosis and, therefore, there is a constant need to find new prognostic markers, as well as markers that can be used as targets for innovative therapeutics. Recently, the search for new biomarkers has turned researchers' attention towards non-coding RNAs, especially long non-coding RNAs (lncRNAs) and micro RNAs (miRNAs). We investigated the expression level of growth arrest-specific transcript 5 (GAS5) lncRNA in 94 younger AML patients, and also the expression level of miR-222 in a cohort of 39 AML patients with normal karyotype (AML-NK), in order to examine their prognostic potential. Our results showed that GAS5 expression level in AML patients was lower compared to healthy controls. Lower GAS5 expression on diagnosis was related to an adverse prognosis. In the AML-NK group patients had higher expression of miR-222 compared to healthy controls. A synergistic effect of GAS5(low)/miR-222(high) status on disease prognosis was not established. This is the first study focused on examining the GAS5 and miR-222 expression pattern in AML patients. Its initial findings indicate the need for further investigation of these two non-coding RNAs, their potential roles in leukemogenesis, and the prognosis of AML patients.
PB  - MDPI, Basel
T2  - Diagnostics
T1  - Expression Profiles of Long Non-Coding RNA GAS5 and MicroRNA-222 in Younger AML Patients
IS  - 1
VL  - 12
DO  - 10.3390/diagnostics12010086
ER  - 
@article{
author = "Pavlović, Đorđe and Tošić, Nataša and Zukić, Branka and Pravdić, Zlatko and Suvajdžić-Vuković, Nada and Pavlović, Sonja and Gašić, Vladimir",
year = "2022",
abstract = "Acute myeloid leukemia (AML) is a heterogeneous malignant disease both on clinical and genetic levels. AML has poor prognosis and, therefore, there is a constant need to find new prognostic markers, as well as markers that can be used as targets for innovative therapeutics. Recently, the search for new biomarkers has turned researchers' attention towards non-coding RNAs, especially long non-coding RNAs (lncRNAs) and micro RNAs (miRNAs). We investigated the expression level of growth arrest-specific transcript 5 (GAS5) lncRNA in 94 younger AML patients, and also the expression level of miR-222 in a cohort of 39 AML patients with normal karyotype (AML-NK), in order to examine their prognostic potential. Our results showed that GAS5 expression level in AML patients was lower compared to healthy controls. Lower GAS5 expression on diagnosis was related to an adverse prognosis. In the AML-NK group patients had higher expression of miR-222 compared to healthy controls. A synergistic effect of GAS5(low)/miR-222(high) status on disease prognosis was not established. This is the first study focused on examining the GAS5 and miR-222 expression pattern in AML patients. Its initial findings indicate the need for further investigation of these two non-coding RNAs, their potential roles in leukemogenesis, and the prognosis of AML patients.",
publisher = "MDPI, Basel",
journal = "Diagnostics",
title = "Expression Profiles of Long Non-Coding RNA GAS5 and MicroRNA-222 in Younger AML Patients",
number = "1",
volume = "12",
doi = "10.3390/diagnostics12010086"
}
Pavlović, Đ., Tošić, N., Zukić, B., Pravdić, Z., Suvajdžić-Vuković, N., Pavlović, S.,& Gašić, V.. (2022). Expression Profiles of Long Non-Coding RNA GAS5 and MicroRNA-222 in Younger AML Patients. in Diagnostics
MDPI, Basel., 12(1).
https://doi.org/10.3390/diagnostics12010086
Pavlović Đ, Tošić N, Zukić B, Pravdić Z, Suvajdžić-Vuković N, Pavlović S, Gašić V. Expression Profiles of Long Non-Coding RNA GAS5 and MicroRNA-222 in Younger AML Patients. in Diagnostics. 2022;12(1).
doi:10.3390/diagnostics12010086 .
Pavlović, Đorđe, Tošić, Nataša, Zukić, Branka, Pravdić, Zlatko, Suvajdžić-Vuković, Nada, Pavlović, Sonja, Gašić, Vladimir, "Expression Profiles of Long Non-Coding RNA GAS5 and MicroRNA-222 in Younger AML Patients" in Diagnostics, 12, no. 1 (2022),
https://doi.org/10.3390/diagnostics12010086 . .
2
5
4

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 . .

Duga nekodirajuća rnk gaS kao novi biomarker u onkologiji

Gašić, Vladimir; Tošić, Nataša

(Beograd : Institut za molekularnu genetiku i genetičko inženjerstvo, 2021)

TY  - CHAP
AU  - Gašić, Vladimir
AU  - Tošić, Nataša
PY  - 2021
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/1727
AB  - Growth arrest specific 5 (GAS5) je duga nekodirajuća RNK koja zaustavlja ćelijski ciklus i promoviše apoptozu.
Ponašajući se kao signalni protein, kao mamac za druge molekule ili kao transportni molekul, ova regulatorna
RNK utiče na niz puteva i molekula koji su bitni za rast ćelije i apoptozu, među kojima se ističu p53 mreža,
mTOR signalni put, AKT signalni put, kao i molekuli mikro RNK, PTEN i slični. Brojne studije na različitim tipovima
karcinoma su pokazale da nivo ekspresije GAS5 utiče na razvoj i tok bolesti kod hematoloških maligniteta,
ginekoloških karcinoma, glioma, karcinoma dojke, karcinoma gastrointestinalnog trakta, bubrega,
bešike, prostate i pluća. Shodno tome, GAS5 je novi biomarker u onkologiji, koji ima dijagnostički i prognostički
značaj.
AB  - Growth arrest specific 5 (GAS5) is a long noncoding RNA which halts the cell cycle and promotes apoptosis.
Acting as a signal protein, as a decoy for other molecules or as a transport molecule, this regulatory RNA influences
a number of pathways and molecules relevant for the growth of the cell and apoptosis, among
them the most important being the p53 network, the mTOR signal pathway, the AKT signal pathway, as well
as molecules of microRNA, PTEN and others.
Numerous studies on diverse cancer types have confirmed that the expression of GAS5 influences the development
and the course of hematological malignancies, gynecologic carcinoma, gliomas, breast cancer,
gastrointestinal cancer, kidney cancer, bladder cancer, prostate cancer and lung cancer. Therefore, GAS5 is
a promising new diagnostic and prognostic biomarker in oncology.
PB  - Beograd : Institut za molekularnu genetiku i genetičko inženjerstvo
T2  - Trendovi u molekularnoj Biologiji
T1  - Duga nekodirajuća rnk gaS kao novi biomarker u onkologiji
T1  - long noncoding rna gaS as a new biomarker in oncology
EP  - 122
SP  - 113
UR  - https://hdl.handle.net/21.15107/rcub_imagine_1727
ER  - 
@inbook{
author = "Gašić, Vladimir and Tošić, Nataša",
year = "2021",
abstract = "Growth arrest specific 5 (GAS5) je duga nekodirajuća RNK koja zaustavlja ćelijski ciklus i promoviše apoptozu.
Ponašajući se kao signalni protein, kao mamac za druge molekule ili kao transportni molekul, ova regulatorna
RNK utiče na niz puteva i molekula koji su bitni za rast ćelije i apoptozu, među kojima se ističu p53 mreža,
mTOR signalni put, AKT signalni put, kao i molekuli mikro RNK, PTEN i slični. Brojne studije na različitim tipovima
karcinoma su pokazale da nivo ekspresije GAS5 utiče na razvoj i tok bolesti kod hematoloških maligniteta,
ginekoloških karcinoma, glioma, karcinoma dojke, karcinoma gastrointestinalnog trakta, bubrega,
bešike, prostate i pluća. Shodno tome, GAS5 je novi biomarker u onkologiji, koji ima dijagnostički i prognostički
značaj., Growth arrest specific 5 (GAS5) is a long noncoding RNA which halts the cell cycle and promotes apoptosis.
Acting as a signal protein, as a decoy for other molecules or as a transport molecule, this regulatory RNA influences
a number of pathways and molecules relevant for the growth of the cell and apoptosis, among
them the most important being the p53 network, the mTOR signal pathway, the AKT signal pathway, as well
as molecules of microRNA, PTEN and others.
Numerous studies on diverse cancer types have confirmed that the expression of GAS5 influences the development
and the course of hematological malignancies, gynecologic carcinoma, gliomas, breast cancer,
gastrointestinal cancer, kidney cancer, bladder cancer, prostate cancer and lung cancer. Therefore, GAS5 is
a promising new diagnostic and prognostic biomarker in oncology.",
publisher = "Beograd : Institut za molekularnu genetiku i genetičko inženjerstvo",
journal = "Trendovi u molekularnoj Biologiji",
booktitle = "Duga nekodirajuća rnk gaS kao novi biomarker u onkologiji, long noncoding rna gaS as a new biomarker in oncology",
pages = "122-113",
url = "https://hdl.handle.net/21.15107/rcub_imagine_1727"
}
Gašić, V.,& Tošić, N.. (2021). Duga nekodirajuća rnk gaS kao novi biomarker u onkologiji. in Trendovi u molekularnoj Biologiji
Beograd : Institut za molekularnu genetiku i genetičko inženjerstvo., 113-122.
https://hdl.handle.net/21.15107/rcub_imagine_1727
Gašić V, Tošić N. Duga nekodirajuća rnk gaS kao novi biomarker u onkologiji. in Trendovi u molekularnoj Biologiji. 2021;:113-122.
https://hdl.handle.net/21.15107/rcub_imagine_1727 .
Gašić, Vladimir, Tošić, Nataša, "Duga nekodirajuća rnk gaS kao novi biomarker u onkologiji" in Trendovi u molekularnoj Biologiji (2021):113-122,
https://hdl.handle.net/21.15107/rcub_imagine_1727 .

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

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

Expression pattern of circulating long non-coding RNA GAS5 as a novel biomarker in non-small cell lung cancer patients

Vesovic, Natasa; Tošić, Nataša; Karan-Đurašević, Teodora; Andric, Zoran; Zdravkovic, Darko; Pavlović, Sonja; Jovanovic, Dragana

(2020)

TY  - JOUR
AU  - Vesovic, Natasa
AU  - Tošić, Nataša
AU  - Karan-Đurašević, Teodora
AU  - Andric, Zoran
AU  - Zdravkovic, Darko
AU  - Pavlović, Sonja
AU  - Jovanovic, Dragana
PY  - 2020
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/1642
AB  - Introduction:  The finding that long noncoding RNAs (lncRNAs) originating from tumor cells could be found in general circulation has prompted the idea to use lncRNAs as noninvasive diagnostic biomarkers of particular diseases. In this study we explored the expression pattern of circulating GAS5...
T2  - Archives of Medical Science
T2  - Archives of Medical ScienceArch Med Sci
T1  - Expression pattern of circulating long non-coding RNA GAS5 as a novel biomarker in non-small cell lung cancer patients
EP  - 7
SP  - 1
DO  - 10.5114/aoms.2020.98815
ER  - 
@article{
author = "Vesovic, Natasa and Tošić, Nataša and Karan-Đurašević, Teodora and Andric, Zoran and Zdravkovic, Darko and Pavlović, Sonja and Jovanovic, Dragana",
year = "2020",
abstract = "Introduction:  The finding that long noncoding RNAs (lncRNAs) originating from tumor cells could be found in general circulation has prompted the idea to use lncRNAs as noninvasive diagnostic biomarkers of particular diseases. In this study we explored the expression pattern of circulating GAS5...",
journal = "Archives of Medical Science, Archives of Medical ScienceArch Med Sci",
title = "Expression pattern of circulating long non-coding RNA GAS5 as a novel biomarker in non-small cell lung cancer patients",
pages = "7-1",
doi = "10.5114/aoms.2020.98815"
}
Vesovic, N., Tošić, N., Karan-Đurašević, T., Andric, Z., Zdravkovic, D., Pavlović, S.,& Jovanovic, D.. (2020). Expression pattern of circulating long non-coding RNA GAS5 as a novel biomarker in non-small cell lung cancer patients. in Archives of Medical Science, 1-7.
https://doi.org/10.5114/aoms.2020.98815
Vesovic N, Tošić N, Karan-Đurašević T, Andric Z, Zdravkovic D, Pavlović S, Jovanovic D. Expression pattern of circulating long non-coding RNA GAS5 as a novel biomarker in non-small cell lung cancer patients. in Archives of Medical Science. 2020;:1-7.
doi:10.5114/aoms.2020.98815 .
Vesovic, Natasa, Tošić, Nataša, Karan-Đurašević, Teodora, Andric, Zoran, Zdravkovic, Darko, Pavlović, Sonja, Jovanovic, Dragana, "Expression pattern of circulating long non-coding RNA GAS5 as a novel biomarker in non-small cell lung cancer patients" in Archives of Medical Science (2020):1-7,
https://doi.org/10.5114/aoms.2020.98815 . .
3

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
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2