Mihaljević, Biljana

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  • Mihaljević, Biljana (7)
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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 . .
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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 . .
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The Role of Lymphocyte to Monocyte Ratio, Microvessel Density and HiGH CD44 Tumor Cell Expression in Non Hodgkin Lymphomas

Jelicić, Jelena; Todorovic-Balint, Milena; Perunicić-Jovanović, Maja; Boricić, Novica; Micev, Marjan; Stojsić, Jelena; Antić, Darko; Anđelić, Boško; Bila, Jelena; Balint, Bela; Pavlović, Sonja; Mihaljević, Biljana

(Springer, Dordrecht, 2016)

TY  - JOUR
AU  - Jelicić, Jelena
AU  - Todorovic-Balint, Milena
AU  - Perunicić-Jovanović, Maja
AU  - Boricić, Novica
AU  - Micev, Marjan
AU  - Stojsić, Jelena
AU  - Antić, Darko
AU  - Anđelić, Boško
AU  - Bila, Jelena
AU  - Balint, Bela
AU  - Pavlović, Sonja
AU  - Mihaljević, Biljana
PY  - 2016
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/944
AB  - Prognostic significance of immune microenvironment has been emphasized using the most advanced analysis, with consecutive attempts to reveal prognostic impact of this findings. The aim of this study was to compare and define prognostic significance of clinical parameters, microvessel density (MVD) in tumour tissue and expression of CD44s as adhesive molecule on tumour cells in diffuse large B cell lymphoma-DLBCL, primary central nervous system DLBCL-CNS DLBCL and follicular lymphoma-FL. A total of 202 histopathological samples (115 DLBCL/65 FL/22 CNS DLBCL) were evaluated. Overall response (complete/partial remission) was achieved in 81.3 % DLBCL patients, 81.8 % primary CNS DLBCL and 92.3 % FL. Absolute lymphocyte count-ALC/Absolute monocyte count-AMC  gt  2.6 in DLBCL and ALC/AMC a parts per thousand yenaEuro parts per thousand 4.7 in FL were associated with better event-free survival (EFS) and overall survival (OS) (p  lt  0.05). In DLBCL, MVD  gt  42 blood vessels/0.36 mm(2) correlated with primary resistant disease (p  lt  0.0001), poorer EFS and OS (p = 0.014). High CD44s expression in FL correlated with inferior EFS and OS (p  lt  0.01). In DLBCL, multivariate Cox regression analysis showed that ALC/AMC was independent parameter that affected OS (HR 3.27, 95 % CI 1.51-7.09, p = 0.003) along with the NCCN-IPI (HR 1.39, 95 % CI 1.08-1.79, p = 0.01). Furthermore, in FL, ALC/AMC mostly influenced OS (HR 5.21, 95 % CI 1.17-23.21, p = 0.03), followed with the FLIPI (HR 3.98, 95 % CI 1.06-14.95, p = 0.041). In DLBCL and FL, ALC/AMC is simple and robust tool that is, with current prognostic scores, able to define long-term survival and identify patients with inferior outcome. The introduction of immunochemotherapy might altered the prognostic significance of microenvionmental biomarkers (MVD and CD44s).
PB  - Springer, Dordrecht
T2  - Pathology & Oncology Research
T1  - The Role of Lymphocyte to Monocyte Ratio, Microvessel Density and HiGH CD44 Tumor Cell Expression in Non Hodgkin Lymphomas
EP  - 577
IS  - 3
SP  - 567
VL  - 22
DO  - 10.1007/s12253-015-0032-7
ER  - 
@article{
author = "Jelicić, Jelena and Todorovic-Balint, Milena and Perunicić-Jovanović, Maja and Boricić, Novica and Micev, Marjan and Stojsić, Jelena and Antić, Darko and Anđelić, Boško and Bila, Jelena and Balint, Bela and Pavlović, Sonja and Mihaljević, Biljana",
year = "2016",
abstract = "Prognostic significance of immune microenvironment has been emphasized using the most advanced analysis, with consecutive attempts to reveal prognostic impact of this findings. The aim of this study was to compare and define prognostic significance of clinical parameters, microvessel density (MVD) in tumour tissue and expression of CD44s as adhesive molecule on tumour cells in diffuse large B cell lymphoma-DLBCL, primary central nervous system DLBCL-CNS DLBCL and follicular lymphoma-FL. A total of 202 histopathological samples (115 DLBCL/65 FL/22 CNS DLBCL) were evaluated. Overall response (complete/partial remission) was achieved in 81.3 % DLBCL patients, 81.8 % primary CNS DLBCL and 92.3 % FL. Absolute lymphocyte count-ALC/Absolute monocyte count-AMC  gt  2.6 in DLBCL and ALC/AMC a parts per thousand yenaEuro parts per thousand 4.7 in FL were associated with better event-free survival (EFS) and overall survival (OS) (p  lt  0.05). In DLBCL, MVD  gt  42 blood vessels/0.36 mm(2) correlated with primary resistant disease (p  lt  0.0001), poorer EFS and OS (p = 0.014). High CD44s expression in FL correlated with inferior EFS and OS (p  lt  0.01). In DLBCL, multivariate Cox regression analysis showed that ALC/AMC was independent parameter that affected OS (HR 3.27, 95 % CI 1.51-7.09, p = 0.003) along with the NCCN-IPI (HR 1.39, 95 % CI 1.08-1.79, p = 0.01). Furthermore, in FL, ALC/AMC mostly influenced OS (HR 5.21, 95 % CI 1.17-23.21, p = 0.03), followed with the FLIPI (HR 3.98, 95 % CI 1.06-14.95, p = 0.041). In DLBCL and FL, ALC/AMC is simple and robust tool that is, with current prognostic scores, able to define long-term survival and identify patients with inferior outcome. The introduction of immunochemotherapy might altered the prognostic significance of microenvionmental biomarkers (MVD and CD44s).",
publisher = "Springer, Dordrecht",
journal = "Pathology & Oncology Research",
title = "The Role of Lymphocyte to Monocyte Ratio, Microvessel Density and HiGH CD44 Tumor Cell Expression in Non Hodgkin Lymphomas",
pages = "577-567",
number = "3",
volume = "22",
doi = "10.1007/s12253-015-0032-7"
}
Jelicić, J., Todorovic-Balint, M., Perunicić-Jovanović, M., Boricić, N., Micev, M., Stojsić, J., Antić, D., Anđelić, B., Bila, J., Balint, B., Pavlović, S.,& Mihaljević, B.. (2016). The Role of Lymphocyte to Monocyte Ratio, Microvessel Density and HiGH CD44 Tumor Cell Expression in Non Hodgkin Lymphomas. in Pathology & Oncology Research
Springer, Dordrecht., 22(3), 567-577.
https://doi.org/10.1007/s12253-015-0032-7
Jelicić J, Todorovic-Balint M, Perunicić-Jovanović M, Boricić N, Micev M, Stojsić J, Antić D, Anđelić B, Bila J, Balint B, Pavlović S, Mihaljević B. The Role of Lymphocyte to Monocyte Ratio, Microvessel Density and HiGH CD44 Tumor Cell Expression in Non Hodgkin Lymphomas. in Pathology & Oncology Research. 2016;22(3):567-577.
doi:10.1007/s12253-015-0032-7 .
Jelicić, Jelena, Todorovic-Balint, Milena, Perunicić-Jovanović, Maja, Boricić, Novica, Micev, Marjan, Stojsić, Jelena, Antić, Darko, Anđelić, Boško, Bila, Jelena, Balint, Bela, Pavlović, Sonja, Mihaljević, Biljana, "The Role of Lymphocyte to Monocyte Ratio, Microvessel Density and HiGH CD44 Tumor Cell Expression in Non Hodgkin Lymphomas" in Pathology & Oncology Research, 22, no. 3 (2016):567-577,
https://doi.org/10.1007/s12253-015-0032-7 . .
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Gene Mutation Profiles in Primary Diffuse Large B Cell Lymphoma of Central Nervous System: Next Generation Sequencing Analyses

Todorovic-Balint, Milena; Jelicić, Jelena; Mihaljević, Biljana; Kostić, Jelena; Stanić, Bojana; Balint, Bela; Pejanović, Nadja; Lucić, Bojana; Tošić, Nataša; Marjanović, Irena; Stojiljković, Maja; Karan-Đurašević, Teodora; Perisić, Ognjen; Rakocević, Goran; Popović, Milos; Raicević, Sava; Bila, Jelena; Antić, Darko; Anđelić, Boško; Pavlović, Sonja

(MDPI, Basel, 2016)

TY  - JOUR
AU  - Todorovic-Balint, Milena
AU  - Jelicić, Jelena
AU  - Mihaljević, Biljana
AU  - Kostić, Jelena
AU  - Stanić, Bojana
AU  - Balint, Bela
AU  - Pejanović, Nadja
AU  - Lucić, Bojana
AU  - Tošić, Nataša
AU  - Marjanović, Irena
AU  - Stojiljković, Maja
AU  - Karan-Đurašević, Teodora
AU  - Perisić, Ognjen
AU  - Rakocević, Goran
AU  - Popović, Milos
AU  - Raicević, Sava
AU  - Bila, Jelena
AU  - Antić, Darko
AU  - Anđelić, Boško
AU  - Pavlović, Sonja
PY  - 2016
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/936
AB  - The existence of a potential primary central nervous system lymphoma-specific genomic signature that differs from the systemic form of diffuse large B cell lymphoma (DLBCL) has been suggested, but is still controversial. We investigated 19 patients with primary DLBCL of central nervous system (DLBCL CNS) using the TruSeq Amplicon Cancer Panel (TSACP) for 48 cancer-related genes. Next generation sequencing (NGS) analyses have revealed that over 80% of potentially protein-changing mutations were located in eight genes (CTNNB1, PIK3CA, PTEN, ATM, KRAS, PTPN11, TP53 and JAK3), pointing to the potential role of these genes in lymphomagenesis. TP53 was the only gene harboring mutations in all 19 patients. In addition, the presence of mutated TP53 and ATM genes correlated with a higher total number of mutations in other analyzed genes. Furthermore, the presence of mutated ATM correlated with poorer event-free survival (EFS) (p = 0.036). The presence of the mutated SMO gene correlated with earlier disease relapse (p = 0.023), inferior event-free survival (p = 0.011) and overall survival (OS) (p = 0.017), while mutations in the PTEN gene were associated with inferior OS (p = 0.048). Our findings suggest that the TP53 and ATM genes could be involved in the molecular pathophysiology of primary DLBCL CNS, whereas mutations in the PTEN and SMO genes could affect survival regardless of the initial treatment approach.
PB  - MDPI, Basel
T2  - International Journal of Molecular Sciences
T1  - Gene Mutation Profiles in Primary Diffuse Large B Cell Lymphoma of Central Nervous System: Next Generation Sequencing Analyses
IS  - 5
VL  - 17
DO  - 10.3390/ijms17050683
ER  - 
@article{
author = "Todorovic-Balint, Milena and Jelicić, Jelena and Mihaljević, Biljana and Kostić, Jelena and Stanić, Bojana and Balint, Bela and Pejanović, Nadja and Lucić, Bojana and Tošić, Nataša and Marjanović, Irena and Stojiljković, Maja and Karan-Đurašević, Teodora and Perisić, Ognjen and Rakocević, Goran and Popović, Milos and Raicević, Sava and Bila, Jelena and Antić, Darko and Anđelić, Boško and Pavlović, Sonja",
year = "2016",
abstract = "The existence of a potential primary central nervous system lymphoma-specific genomic signature that differs from the systemic form of diffuse large B cell lymphoma (DLBCL) has been suggested, but is still controversial. We investigated 19 patients with primary DLBCL of central nervous system (DLBCL CNS) using the TruSeq Amplicon Cancer Panel (TSACP) for 48 cancer-related genes. Next generation sequencing (NGS) analyses have revealed that over 80% of potentially protein-changing mutations were located in eight genes (CTNNB1, PIK3CA, PTEN, ATM, KRAS, PTPN11, TP53 and JAK3), pointing to the potential role of these genes in lymphomagenesis. TP53 was the only gene harboring mutations in all 19 patients. In addition, the presence of mutated TP53 and ATM genes correlated with a higher total number of mutations in other analyzed genes. Furthermore, the presence of mutated ATM correlated with poorer event-free survival (EFS) (p = 0.036). The presence of the mutated SMO gene correlated with earlier disease relapse (p = 0.023), inferior event-free survival (p = 0.011) and overall survival (OS) (p = 0.017), while mutations in the PTEN gene were associated with inferior OS (p = 0.048). Our findings suggest that the TP53 and ATM genes could be involved in the molecular pathophysiology of primary DLBCL CNS, whereas mutations in the PTEN and SMO genes could affect survival regardless of the initial treatment approach.",
publisher = "MDPI, Basel",
journal = "International Journal of Molecular Sciences",
title = "Gene Mutation Profiles in Primary Diffuse Large B Cell Lymphoma of Central Nervous System: Next Generation Sequencing Analyses",
number = "5",
volume = "17",
doi = "10.3390/ijms17050683"
}
Todorovic-Balint, M., Jelicić, J., Mihaljević, B., Kostić, J., Stanić, B., Balint, B., Pejanović, N., Lucić, B., Tošić, N., Marjanović, I., Stojiljković, M., Karan-Đurašević, T., Perisić, O., Rakocević, G., Popović, M., Raicević, S., Bila, J., Antić, D., Anđelić, B.,& Pavlović, S.. (2016). Gene Mutation Profiles in Primary Diffuse Large B Cell Lymphoma of Central Nervous System: Next Generation Sequencing Analyses. in International Journal of Molecular Sciences
MDPI, Basel., 17(5).
https://doi.org/10.3390/ijms17050683
Todorovic-Balint M, Jelicić J, Mihaljević B, Kostić J, Stanić B, Balint B, Pejanović N, Lucić B, Tošić N, Marjanović I, Stojiljković M, Karan-Đurašević T, Perisić O, Rakocević G, Popović M, Raicević S, Bila J, Antić D, Anđelić B, Pavlović S. Gene Mutation Profiles in Primary Diffuse Large B Cell Lymphoma of Central Nervous System: Next Generation Sequencing Analyses. in International Journal of Molecular Sciences. 2016;17(5).
doi:10.3390/ijms17050683 .
Todorovic-Balint, Milena, Jelicić, Jelena, Mihaljević, Biljana, Kostić, Jelena, Stanić, Bojana, Balint, Bela, Pejanović, Nadja, Lucić, Bojana, Tošić, Nataša, Marjanović, Irena, Stojiljković, Maja, Karan-Đurašević, Teodora, Perisić, Ognjen, Rakocević, Goran, Popović, Milos, Raicević, Sava, Bila, Jelena, Antić, Darko, Anđelić, Boško, Pavlović, Sonja, "Gene Mutation Profiles in Primary Diffuse Large B Cell Lymphoma of Central Nervous System: Next Generation Sequencing Analyses" in International Journal of Molecular Sciences, 17, no. 5 (2016),
https://doi.org/10.3390/ijms17050683 . .
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Prognostic Significance of Cereblon Expression in Patients With Multiple Myeloma

Bila, Jelena; Sretenović, Aleksandra; Jelicić, Jelena; Tošić, Nataša; Marjanović, Irena; Fekete, Marija Dencic; Antić, Darko; Todorovic-Balint, Milena; Marković, Olivera; Milojević, Zoran; Radojković, Milica; Trajković, Goran; Purić, Mila; Pavlović, Sonja; Mihaljević, Biljana

(CIG Media Group, Lp, Dallas, 2016)

TY  - JOUR
AU  - Bila, Jelena
AU  - Sretenović, Aleksandra
AU  - Jelicić, Jelena
AU  - Tošić, Nataša
AU  - Marjanović, Irena
AU  - Fekete, Marija Dencic
AU  - Antić, Darko
AU  - Todorovic-Balint, Milena
AU  - Marković, Olivera
AU  - Milojević, Zoran
AU  - Radojković, Milica
AU  - Trajković, Goran
AU  - Purić, Mila
AU  - Pavlović, Sonja
AU  - Mihaljević, Biljana
PY  - 2016
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/962
AB  - Within a personalized treatment approach in multiple myeloma (MM), the prognostic significance of cereblon (CRBN) expression was analyzed in 92 newly diagnosed patients. In patients treated with thalidomide-based combinations, CRBN expression significantly affected the treatment response (P = .028) and progression free survival (P = .017). With implications for the treatment outcome, measurement of CRBN expression might represent an additional prognostic tool in a personalized treatment approach. Background: To personalize the treatment approach for patients with multiple myeloma (MM), molecular markers such as cereblon (CRBN) are currently the focus of investigation. The aim of the present study was to test the prognostic significance of CRBN expression in MM patients ineligible for autologous stem cell transplantation (ASCT). Patients and Methods: The data from 92 previously untreated patients were analyzed. The distribution according to the International Staging System score was 26.1%, 30.4%, and 43.5% with a score of 1, 2, and 3, respectively. Thalidomide- and bortezomib-based combinations were used in 83.7% and 16.3% of the patients, respectively. Results: A treatment response (complete remission, very good partial remission, partial remission) was achieved in 83.7% of the patients and correlated with high CRBN expression (P = .006), mainly in the patients treated with thalidomide (P = .028). Low CRBN expression affected progression-free survival (PFS; P = .017) but not overall survival (OS) in patients treated with thalidomide and had no influence on OS in the bortezomib group. In the Cox regression model, low CRBN expression was the most important prognostic parameter that influenced PFS in the thalidomide-treated patients (P = .012). Conclusion: CRBN expression is of prognostic value in MM patients ineligible for ASCT treated with thalidomide as an immunomodulatory drug. With low expression indicating a possible suboptimal treatment outcome, measurement of CRBN expression might serve as additional prognostic tool in the personalized treatment approach.
PB  - CIG Media Group, Lp, Dallas
T2  - Clinical Lymphoma Myeloma & Leukemia
T1  - Prognostic Significance of Cereblon Expression in Patients With Multiple Myeloma
EP  - 615
IS  - 11
SP  - 610
VL  - 16
DO  - 10.1016/j.clml.2016.08.007
ER  - 
@article{
author = "Bila, Jelena and Sretenović, Aleksandra and Jelicić, Jelena and Tošić, Nataša and Marjanović, Irena and Fekete, Marija Dencic and Antić, Darko and Todorovic-Balint, Milena and Marković, Olivera and Milojević, Zoran and Radojković, Milica and Trajković, Goran and Purić, Mila and Pavlović, Sonja and Mihaljević, Biljana",
year = "2016",
abstract = "Within a personalized treatment approach in multiple myeloma (MM), the prognostic significance of cereblon (CRBN) expression was analyzed in 92 newly diagnosed patients. In patients treated with thalidomide-based combinations, CRBN expression significantly affected the treatment response (P = .028) and progression free survival (P = .017). With implications for the treatment outcome, measurement of CRBN expression might represent an additional prognostic tool in a personalized treatment approach. Background: To personalize the treatment approach for patients with multiple myeloma (MM), molecular markers such as cereblon (CRBN) are currently the focus of investigation. The aim of the present study was to test the prognostic significance of CRBN expression in MM patients ineligible for autologous stem cell transplantation (ASCT). Patients and Methods: The data from 92 previously untreated patients were analyzed. The distribution according to the International Staging System score was 26.1%, 30.4%, and 43.5% with a score of 1, 2, and 3, respectively. Thalidomide- and bortezomib-based combinations were used in 83.7% and 16.3% of the patients, respectively. Results: A treatment response (complete remission, very good partial remission, partial remission) was achieved in 83.7% of the patients and correlated with high CRBN expression (P = .006), mainly in the patients treated with thalidomide (P = .028). Low CRBN expression affected progression-free survival (PFS; P = .017) but not overall survival (OS) in patients treated with thalidomide and had no influence on OS in the bortezomib group. In the Cox regression model, low CRBN expression was the most important prognostic parameter that influenced PFS in the thalidomide-treated patients (P = .012). Conclusion: CRBN expression is of prognostic value in MM patients ineligible for ASCT treated with thalidomide as an immunomodulatory drug. With low expression indicating a possible suboptimal treatment outcome, measurement of CRBN expression might serve as additional prognostic tool in the personalized treatment approach.",
publisher = "CIG Media Group, Lp, Dallas",
journal = "Clinical Lymphoma Myeloma & Leukemia",
title = "Prognostic Significance of Cereblon Expression in Patients With Multiple Myeloma",
pages = "615-610",
number = "11",
volume = "16",
doi = "10.1016/j.clml.2016.08.007"
}
Bila, J., Sretenović, A., Jelicić, J., Tošić, N., Marjanović, I., Fekete, M. D., Antić, D., Todorovic-Balint, M., Marković, O., Milojević, Z., Radojković, M., Trajković, G., Purić, M., Pavlović, S.,& Mihaljević, B.. (2016). Prognostic Significance of Cereblon Expression in Patients With Multiple Myeloma. in Clinical Lymphoma Myeloma & Leukemia
CIG Media Group, Lp, Dallas., 16(11), 610-615.
https://doi.org/10.1016/j.clml.2016.08.007
Bila J, Sretenović A, Jelicić J, Tošić N, Marjanović I, Fekete MD, Antić D, Todorovic-Balint M, Marković O, Milojević Z, Radojković M, Trajković G, Purić M, Pavlović S, Mihaljević B. Prognostic Significance of Cereblon Expression in Patients With Multiple Myeloma. in Clinical Lymphoma Myeloma & Leukemia. 2016;16(11):610-615.
doi:10.1016/j.clml.2016.08.007 .
Bila, Jelena, Sretenović, Aleksandra, Jelicić, Jelena, Tošić, Nataša, Marjanović, Irena, Fekete, Marija Dencic, Antić, Darko, Todorovic-Balint, Milena, Marković, Olivera, Milojević, Zoran, Radojković, Milica, Trajković, Goran, Purić, Mila, Pavlović, Sonja, Mihaljević, Biljana, "Prognostic Significance of Cereblon Expression in Patients With Multiple Myeloma" in Clinical Lymphoma Myeloma & Leukemia, 16, no. 11 (2016):610-615,
https://doi.org/10.1016/j.clml.2016.08.007 . .
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11

Mutational Status and Gene Repertoire of IGHV-IGHD-IGHJ Rearrangements in Serbian Patients With Chronic Lymphocytic Leukemia

Karan-Đurašević, Teodora; Palibrk, Vuk; Kostić, Tatjana; Spasovski, Vesna; Nikčević, Gordana; Srzentić Dražilov, Sanja; Colović, Milica; Čolović, Nataša; Vidović, Ana; Antić, Darko; Mihaljević, Biljana; Pavlović, Sonja; Tošić, Nataša

(CIG Media Group, Lp, Dallas, 2012)

TY  - JOUR
AU  - Karan-Đurašević, Teodora
AU  - Palibrk, Vuk
AU  - Kostić, Tatjana
AU  - Spasovski, Vesna
AU  - Nikčević, Gordana
AU  - Srzentić Dražilov, Sanja
AU  - Colović, Milica
AU  - Čolović, Nataša
AU  - Vidović, Ana
AU  - Antić, Darko
AU  - Mihaljević, Biljana
AU  - Pavlović, Sonja
AU  - Tošić, Nataša
PY  - 2012
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/565
AB  - The mutational status and configuration of immunoglobulin heavy variable (IGHV) gene rearrangements was analyzed in 85 Serbian patients with chronic lymphocytic leukemia (CLL). We found that 55.3% of cases belonged to mutated and 44.7% to unmutated CLL, progressive disease predominating in the unmutated subset. IGHV gene use resembled that obtained for Mediterranean countries, except for underrepresentation of the IGHV4 subgroup in our cohort. Background: Chronic lymphocytic leukemia (CLL) results from the clonal expansion of mature B lymphocytes and is characterized by extreme clinical heterogeneity. One of the most reliable prognostic markers in chronic lymphocytic leukemia (CLL) is the mutational status of immunoglobulin heavy variable (IGHV) genes, which defines 2 subsets, mutated CLL (M-CLL) and unmutated CLL (U-CLL), with different clinical courses. Biased IGHV gene use between M-CLL and U-CLL clones, as well as population differences in the IGHV gene repertoire have been reported. Patients and Methods: In this study, mutational status and configuration of IGHV-IGHD-IGHJ rearrangements in 85 Serbian patients were analyzed using reverse transcriptase-polymerase chain reaction (RT-PCR) and sequencing methodology. Results: We found that 55.3% of cases belonged to M-CLL and 44.7% belonged to U-CLL, with progressive disease predominating in the unmutated subset. Most frequently expressed was the IGHV3 subgroup (55.7%), followed by IGHV1 (27.3%), IGHV4 (12.5%), IGHV5 (2.3%), IGHV2 (1.1%), and IGHV6 (1.1%). The distribution of IGHD subgroups was as follows: IGHD3, 39.1%; IGHD2, 21.8%; IGHD6, 12.6%; IGHD1, 10.3%; IGHD4, 8%; IGHD5, 6.9%; and IGHD7, 1.1%. The most frequent IGHJ gene was IGHJ4 (48.9%), followed by IGHJ6 (28.4%), IGHJ3 (11.4%), and IGHJ5 (11.4%). In 15.3% of cases, heavy complementarity-determining region 3 (VH CDR3) amino acid sequences could be assigned to previously defined stereotyped clusters. Conclusions: Our study showed a strong correlation between IGHV gene mutational status and clinical course of CLL. IGHV gene use was comparable to that obtained for Mediterranean countries, with the exception of the IGHV4 subgroup, which was underrepresented in our cohort. Clinical Lymphoma, Myeloma & Leukemia, Vol. 12, No. 4, 252-60
PB  - CIG Media Group, Lp, Dallas
T2  - Clinical Lymphoma Myeloma & Leukemia
T1  - Mutational Status and Gene Repertoire of IGHV-IGHD-IGHJ Rearrangements in Serbian Patients With Chronic Lymphocytic Leukemia
EP  - 260
IS  - 4
SP  - 252
VL  - 12
DO  - 10.1016/j.clml.2012.03.005
ER  - 
@article{
author = "Karan-Đurašević, Teodora and Palibrk, Vuk and Kostić, Tatjana and Spasovski, Vesna and Nikčević, Gordana and Srzentić Dražilov, Sanja and Colović, Milica and Čolović, Nataša and Vidović, Ana and Antić, Darko and Mihaljević, Biljana and Pavlović, Sonja and Tošić, Nataša",
year = "2012",
abstract = "The mutational status and configuration of immunoglobulin heavy variable (IGHV) gene rearrangements was analyzed in 85 Serbian patients with chronic lymphocytic leukemia (CLL). We found that 55.3% of cases belonged to mutated and 44.7% to unmutated CLL, progressive disease predominating in the unmutated subset. IGHV gene use resembled that obtained for Mediterranean countries, except for underrepresentation of the IGHV4 subgroup in our cohort. Background: Chronic lymphocytic leukemia (CLL) results from the clonal expansion of mature B lymphocytes and is characterized by extreme clinical heterogeneity. One of the most reliable prognostic markers in chronic lymphocytic leukemia (CLL) is the mutational status of immunoglobulin heavy variable (IGHV) genes, which defines 2 subsets, mutated CLL (M-CLL) and unmutated CLL (U-CLL), with different clinical courses. Biased IGHV gene use between M-CLL and U-CLL clones, as well as population differences in the IGHV gene repertoire have been reported. Patients and Methods: In this study, mutational status and configuration of IGHV-IGHD-IGHJ rearrangements in 85 Serbian patients were analyzed using reverse transcriptase-polymerase chain reaction (RT-PCR) and sequencing methodology. Results: We found that 55.3% of cases belonged to M-CLL and 44.7% belonged to U-CLL, with progressive disease predominating in the unmutated subset. Most frequently expressed was the IGHV3 subgroup (55.7%), followed by IGHV1 (27.3%), IGHV4 (12.5%), IGHV5 (2.3%), IGHV2 (1.1%), and IGHV6 (1.1%). The distribution of IGHD subgroups was as follows: IGHD3, 39.1%; IGHD2, 21.8%; IGHD6, 12.6%; IGHD1, 10.3%; IGHD4, 8%; IGHD5, 6.9%; and IGHD7, 1.1%. The most frequent IGHJ gene was IGHJ4 (48.9%), followed by IGHJ6 (28.4%), IGHJ3 (11.4%), and IGHJ5 (11.4%). In 15.3% of cases, heavy complementarity-determining region 3 (VH CDR3) amino acid sequences could be assigned to previously defined stereotyped clusters. Conclusions: Our study showed a strong correlation between IGHV gene mutational status and clinical course of CLL. IGHV gene use was comparable to that obtained for Mediterranean countries, with the exception of the IGHV4 subgroup, which was underrepresented in our cohort. Clinical Lymphoma, Myeloma & Leukemia, Vol. 12, No. 4, 252-60",
publisher = "CIG Media Group, Lp, Dallas",
journal = "Clinical Lymphoma Myeloma & Leukemia",
title = "Mutational Status and Gene Repertoire of IGHV-IGHD-IGHJ Rearrangements in Serbian Patients With Chronic Lymphocytic Leukemia",
pages = "260-252",
number = "4",
volume = "12",
doi = "10.1016/j.clml.2012.03.005"
}
Karan-Đurašević, T., Palibrk, V., Kostić, T., Spasovski, V., Nikčević, G., Srzentić Dražilov, S., Colović, M., Čolović, N., Vidović, A., Antić, D., Mihaljević, B., Pavlović, S.,& Tošić, N.. (2012). Mutational Status and Gene Repertoire of IGHV-IGHD-IGHJ Rearrangements in Serbian Patients With Chronic Lymphocytic Leukemia. in Clinical Lymphoma Myeloma & Leukemia
CIG Media Group, Lp, Dallas., 12(4), 252-260.
https://doi.org/10.1016/j.clml.2012.03.005
Karan-Đurašević T, Palibrk V, Kostić T, Spasovski V, Nikčević G, Srzentić Dražilov S, Colović M, Čolović N, Vidović A, Antić D, Mihaljević B, Pavlović S, Tošić N. Mutational Status and Gene Repertoire of IGHV-IGHD-IGHJ Rearrangements in Serbian Patients With Chronic Lymphocytic Leukemia. in Clinical Lymphoma Myeloma & Leukemia. 2012;12(4):252-260.
doi:10.1016/j.clml.2012.03.005 .
Karan-Đurašević, Teodora, Palibrk, Vuk, Kostić, Tatjana, Spasovski, Vesna, Nikčević, Gordana, Srzentić Dražilov, Sanja, Colović, Milica, Čolović, Nataša, Vidović, Ana, Antić, Darko, Mihaljević, Biljana, Pavlović, Sonja, Tošić, Nataša, "Mutational Status and Gene Repertoire of IGHV-IGHD-IGHJ Rearrangements in Serbian Patients With Chronic Lymphocytic Leukemia" in Clinical Lymphoma Myeloma & Leukemia, 12, no. 4 (2012):252-260,
https://doi.org/10.1016/j.clml.2012.03.005 . .
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Patients with early stage chronic lymphocytic leukemia: new risk stratification based on molecular profiling

Antić, Darko; Mihaljević, Biljana; Cokić, Vladan; Fekete, Marija Dencic; Karan-Đurašević, Teodora; Pavlović, Sonja; Milić, Nataša; Elezović, Ivo

(Taylor & Francis Ltd, Abingdon, 2011)

TY  - JOUR
AU  - Antić, Darko
AU  - Mihaljević, Biljana
AU  - Cokić, Vladan
AU  - Fekete, Marija Dencic
AU  - Karan-Đurašević, Teodora
AU  - Pavlović, Sonja
AU  - Milić, Nataša
AU  - Elezović, Ivo
PY  - 2011
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/518
AB  - We investigated molecular and biological parameters reflecting the biology of chronic lymphocytic leukemia (CLL) that may help us to predict the time to first treatment (TTT). A group of 33 patients with newly diagnosed CLL (Binet stage A) were analyzed. We developed a new scoring system based on the serum levels of beta(2)-microglobulin (beta M-2) and vascular endothelial growth factor (VEGF) and the expression of lipoprotein lipase (LPL). Patients with a score of 0 had a TTT of 58.4 months, while patients with a score of 3 (increased levels of beta M-2, LPL, and VEGF) had a significantly shorter TTT of only 10.6 months (p  lt  0.0001).
PB  - Taylor & Francis Ltd, Abingdon
T2  - Leukemia & Lymphoma
T1  - Patients with early stage chronic lymphocytic leukemia: new risk stratification based on molecular profiling
EP  - 1397
IS  - 7
SP  - 1394
VL  - 52
DO  - 10.3109/10428194.2011.578311
ER  - 
@article{
author = "Antić, Darko and Mihaljević, Biljana and Cokić, Vladan and Fekete, Marija Dencic and Karan-Đurašević, Teodora and Pavlović, Sonja and Milić, Nataša and Elezović, Ivo",
year = "2011",
abstract = "We investigated molecular and biological parameters reflecting the biology of chronic lymphocytic leukemia (CLL) that may help us to predict the time to first treatment (TTT). A group of 33 patients with newly diagnosed CLL (Binet stage A) were analyzed. We developed a new scoring system based on the serum levels of beta(2)-microglobulin (beta M-2) and vascular endothelial growth factor (VEGF) and the expression of lipoprotein lipase (LPL). Patients with a score of 0 had a TTT of 58.4 months, while patients with a score of 3 (increased levels of beta M-2, LPL, and VEGF) had a significantly shorter TTT of only 10.6 months (p  lt  0.0001).",
publisher = "Taylor & Francis Ltd, Abingdon",
journal = "Leukemia & Lymphoma",
title = "Patients with early stage chronic lymphocytic leukemia: new risk stratification based on molecular profiling",
pages = "1397-1394",
number = "7",
volume = "52",
doi = "10.3109/10428194.2011.578311"
}
Antić, D., Mihaljević, B., Cokić, V., Fekete, M. D., Karan-Đurašević, T., Pavlović, S., Milić, N.,& Elezović, I.. (2011). Patients with early stage chronic lymphocytic leukemia: new risk stratification based on molecular profiling. in Leukemia & Lymphoma
Taylor & Francis Ltd, Abingdon., 52(7), 1394-1397.
https://doi.org/10.3109/10428194.2011.578311
Antić D, Mihaljević B, Cokić V, Fekete MD, Karan-Đurašević T, Pavlović S, Milić N, Elezović I. Patients with early stage chronic lymphocytic leukemia: new risk stratification based on molecular profiling. in Leukemia & Lymphoma. 2011;52(7):1394-1397.
doi:10.3109/10428194.2011.578311 .
Antić, Darko, Mihaljević, Biljana, Cokić, Vladan, Fekete, Marija Dencic, Karan-Đurašević, Teodora, Pavlović, Sonja, Milić, Nataša, Elezović, Ivo, "Patients with early stage chronic lymphocytic leukemia: new risk stratification based on molecular profiling" in Leukemia & Lymphoma, 52, no. 7 (2011):1394-1397,
https://doi.org/10.3109/10428194.2011.578311 . .
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