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

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

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

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

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

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

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

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

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

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

TY  - JOUR
AU  - Virijević, Marijana
AU  - Karan-Đurašević, Teodora
AU  - Marjanović, Irena
AU  - Tošić, Nataša
AU  - Mitrović, Mirjana
AU  - Djunić, Irena
AU  - Čolović, Nataša
AU  - Vidović, Ana
AU  - Suvajdžić-Vuković, Nada
AU  - Tomin, Dragica
AU  - Pavlović, Sonja
PY  - 2016
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/963
AB  - Background. Mutations in the isocitrate dehydrogenase 1 and 2 (IDH1 and IDH2) genes are frequent molecular lesions in acute myeloid leukaemia with normal karyotype (AML-NK). The effects of IDH mutations on clinical features and treatment outcome in AML-NK have been widely investigated, but only a few studies monitored these mutations during follow-up. Patients and methods. In our study samples from 110 adult de novo AML-NK were studied for the presence of IDH1 and IDH2 mutations, their associations with other prognostic markers and disease outcome. We also analyzed the stability of these mutations during the course of the disease in complete remission (CR) and relapse. Results. IDH mutations were found in 25 (23%) patients. IDH+ patients tend to have lower CR rate compared to IDH-patients (44% vs 62.2%, p = 0.152), and had slightly lower disease free survival (12 months vs 17 months; p = 0.091). On the other hand, the presence of IDH mutations had significant impact on overall survival (2 vs 7 months; p = 0.039). The stability of IDH mutations were studied sequentially in 19 IDH+ patients. All of them lost the mutation in CR, and the same IDH mutations were detected in relapsed samples. Conclusions. Our study shows that the presence of IDH mutations confer an adverse effect in AML-NK patients, which in combination with other molecular markers can lead to an improved risk stratification and better treatment. Also, IDH mutations are very stable during the course of the disease and can be potentially used as markers for minimal residual disease detection.
PB  - Walter De Gruyter Gmbh, Berlin
T2  - Radiology and Oncology
T1  - Somatic mutations of isocitrate dehydrogenases 1 and 2 are prognostic and follow-up markers in patients with acute myeloid leukaemia with normal karyotype
EP  - 393
IS  - 4
SP  - 385
VL  - 50
DO  - 10.1515/raon-2016-0044
ER  - 

@article{
author = "Virijević, Marijana and Karan-Đurašević, Teodora and Marjanović, Irena and Tošić, Nataša and Mitrović, Mirjana and Djunić, Irena and Čolović, Nataša and Vidović, Ana and Suvajdžić-Vuković, Nada and Tomin, Dragica and Pavlović, Sonja",
year = "2016",
abstract = "Background. Mutations in the isocitrate dehydrogenase 1 and 2 (IDH1 and IDH2) genes are frequent molecular lesions in acute myeloid leukaemia with normal karyotype (AML-NK). The effects of IDH mutations on clinical features and treatment outcome in AML-NK have been widely investigated, but only a few studies monitored these mutations during follow-up. Patients and methods. In our study samples from 110 adult de novo AML-NK were studied for the presence of IDH1 and IDH2 mutations, their associations with other prognostic markers and disease outcome. We also analyzed the stability of these mutations during the course of the disease in complete remission (CR) and relapse. Results. IDH mutations were found in 25 (23%) patients. IDH+ patients tend to have lower CR rate compared to IDH-patients (44% vs 62.2%, p = 0.152), and had slightly lower disease free survival (12 months vs 17 months; p = 0.091). On the other hand, the presence of IDH mutations had significant impact on overall survival (2 vs 7 months; p = 0.039). The stability of IDH mutations were studied sequentially in 19 IDH+ patients. All of them lost the mutation in CR, and the same IDH mutations were detected in relapsed samples. Conclusions. Our study shows that the presence of IDH mutations confer an adverse effect in AML-NK patients, which in combination with other molecular markers can lead to an improved risk stratification and better treatment. Also, IDH mutations are very stable during the course of the disease and can be potentially used as markers for minimal residual disease detection.",
publisher = "Walter De Gruyter Gmbh, Berlin",
journal = "Radiology and Oncology",
title = "Somatic mutations of isocitrate dehydrogenases 1 and 2 are prognostic and follow-up markers in patients with acute myeloid leukaemia with normal karyotype",
pages = "393-385",
number = "4",
volume = "50",
doi = "10.1515/raon-2016-0044"
}

Virijević, M., Karan-Đurašević, T., Marjanović, I., Tošić, N., Mitrović, M., Djunić, I., Čolović, N., Vidović, A., Suvajdžić-Vuković, N., Tomin, D.,& Pavlović, S.. (2016). Somatic mutations of isocitrate dehydrogenases 1 and 2 are prognostic and follow-up markers in patients with acute myeloid leukaemia with normal karyotype. in Radiology and Oncology
Walter De Gruyter Gmbh, Berlin., 50(4), 385-393.
https://doi.org/10.1515/raon-2016-0044

Virijević M, Karan-Đurašević T, Marjanović I, Tošić N, Mitrović M, Djunić I, Čolović N, Vidović A, Suvajdžić-Vuković N, Tomin D, Pavlović S. Somatic mutations of isocitrate dehydrogenases 1 and 2 are prognostic and follow-up markers in patients with acute myeloid leukaemia with normal karyotype. in Radiology and Oncology. 2016;50(4):385-393.
doi:10.1515/raon-2016-0044 .

Virijević, Marijana, Karan-Đurašević, Teodora, Marjanović, Irena, Tošić, Nataša, Mitrović, Mirjana, Djunić, Irena, Čolović, Nataša, Vidović, Ana, Suvajdžić-Vuković, Nada, Tomin, Dragica, Pavlović, Sonja, "Somatic mutations of isocitrate dehydrogenases 1 and 2 are prognostic and follow-up markers in patients with acute myeloid leukaemia with normal karyotype" in Radiology and Oncology, 50, no. 4 (2016):385-393,
https://doi.org/10.1515/raon-2016-0044 . .

TY  - JOUR
AU  - Mitrović, Mirjana
AU  - Suvajdžić, Nada
AU  - Elezović, Ivo
AU  - Bogdanović, Andrija
AU  - Đorđević, Valentina
AU  - Miljić, Predrag
AU  - Djunić, Irena
AU  - Gvozdenov, Maja
AU  - Čolović, Nataša
AU  - Virijević, Marijana
AU  - Leković, Danijela
AU  - Vidović, Ana
AU  - Tomin, Dragica
PY  - 2015
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/891
AB  - Introduction: Thrombotic events (TE) appear to be more common in acute promyelocytic leukemia (APL) than in other acute leukemias, with reported prevalence ranging from 2 to 10-15%. Materials and Methods: We retrospectively analyzed the data on TE appearance in 63 APL patients. Results: TE occured in 13 (20.6%) cases, four arterial (6.3%) and nine venous (14.3%). TE were more frequently diagnosed after initiation of weekly D-dimer monitoring (7 TE during 20 months vs 6 during 76 months, P = 0.032). Patients with and without venous thrombosis were significantly different regarding female/male ratio (P = 0.046), PT (P = 0.022), a PTT (P = 0.044), ISTH DIC score (P = 0.001), bcr3 (P = 0.02) and FLT3-ITD (P = 0.028) mutation. The most significant risk factor for venous TE occurrence in multivariate analysis was FLT3-ITD mutation (P = 0.034). PAI-1 4G/4G polymorphism was five times more frequent in patients with venous TE than without it (P = 0.05). Regarding risk factors for arterial TE we failed to identify any. Conclusions: We have demonstrated that APL-related TE rate is higher than previously reported and that weekly D-dimer monitoring might help to identify patients with silent thrombosis. Moreover, our study suggests a possible relationship between venous TE occurrence and several laboratory findings (PT, aPTT, ISTH DIC score, bcr3 isoform, FLT3-ITD mutation and PAI 4G/4G). Prophylactic use of heparin might be considered in patients with ISTH DIC score  lt  5, bcr3 isoform, FLT3-ITD mutation and PAI 4G/4G.
PB  - Pergamon-Elsevier Science Ltd, Oxford
T2  - Thrombosis Research
T1  - Thrombotic events in acute promyelocytic leukemia
EP  - 593
IS  - 4
SP  - 588
VL  - 135
DO  - 10.1016/j.thromres.2014.11.026
ER  - 

@article{
author = "Mitrović, Mirjana and Suvajdžić, Nada and Elezović, Ivo and Bogdanović, Andrija and Đorđević, Valentina and Miljić, Predrag and Djunić, Irena and Gvozdenov, Maja and Čolović, Nataša and Virijević, Marijana and Leković, Danijela and Vidović, Ana and Tomin, Dragica",
year = "2015",
abstract = "Introduction: Thrombotic events (TE) appear to be more common in acute promyelocytic leukemia (APL) than in other acute leukemias, with reported prevalence ranging from 2 to 10-15%. Materials and Methods: We retrospectively analyzed the data on TE appearance in 63 APL patients. Results: TE occured in 13 (20.6%) cases, four arterial (6.3%) and nine venous (14.3%). TE were more frequently diagnosed after initiation of weekly D-dimer monitoring (7 TE during 20 months vs 6 during 76 months, P = 0.032). Patients with and without venous thrombosis were significantly different regarding female/male ratio (P = 0.046), PT (P = 0.022), a PTT (P = 0.044), ISTH DIC score (P = 0.001), bcr3 (P = 0.02) and FLT3-ITD (P = 0.028) mutation. The most significant risk factor for venous TE occurrence in multivariate analysis was FLT3-ITD mutation (P = 0.034). PAI-1 4G/4G polymorphism was five times more frequent in patients with venous TE than without it (P = 0.05). Regarding risk factors for arterial TE we failed to identify any. Conclusions: We have demonstrated that APL-related TE rate is higher than previously reported and that weekly D-dimer monitoring might help to identify patients with silent thrombosis. Moreover, our study suggests a possible relationship between venous TE occurrence and several laboratory findings (PT, aPTT, ISTH DIC score, bcr3 isoform, FLT3-ITD mutation and PAI 4G/4G). Prophylactic use of heparin might be considered in patients with ISTH DIC score  lt  5, bcr3 isoform, FLT3-ITD mutation and PAI 4G/4G.",
publisher = "Pergamon-Elsevier Science Ltd, Oxford",
journal = "Thrombosis Research",
title = "Thrombotic events in acute promyelocytic leukemia",
pages = "593-588",
number = "4",
volume = "135",
doi = "10.1016/j.thromres.2014.11.026"
}

Mitrović, M., Suvajdžić, N., Elezović, I., Bogdanović, A., Đorđević, V., Miljić, P., Djunić, I., Gvozdenov, M., Čolović, N., Virijević, M., Leković, D., Vidović, A.,& Tomin, D.. (2015). Thrombotic events in acute promyelocytic leukemia. in Thrombosis Research
Pergamon-Elsevier Science Ltd, Oxford., 135(4), 588-593.
https://doi.org/10.1016/j.thromres.2014.11.026

Mitrović M, Suvajdžić N, Elezović I, Bogdanović A, Đorđević V, Miljić P, Djunić I, Gvozdenov M, Čolović N, Virijević M, Leković D, Vidović A, Tomin D. Thrombotic events in acute promyelocytic leukemia. in Thrombosis Research. 2015;135(4):588-593.
doi:10.1016/j.thromres.2014.11.026 .

Mitrović, Mirjana, Suvajdžić, Nada, Elezović, Ivo, Bogdanović, Andrija, Đorđević, Valentina, Miljić, Predrag, Djunić, Irena, Gvozdenov, Maja, Čolović, Nataša, Virijević, Marijana, Leković, Danijela, Vidović, Ana, Tomin, Dragica, "Thrombotic events in acute promyelocytic leukemia" in Thrombosis Research, 135, no. 4 (2015):588-593,
https://doi.org/10.1016/j.thromres.2014.11.026 . .

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 . .

TY  - JOUR
AU  - Kuzmanović, Milos
AU  - Tošić, Nataša
AU  - Čolović, Nataša
AU  - Karan-Đurašević, Teodora
AU  - Spasovski, Vesna
AU  - Ugrin, Milena
AU  - Nikčević, Gordana
AU  - Suvajdžić-Vuković, Nada
AU  - Tomin, Dragica
AU  - Vidović, Ana
AU  - Virijević, Marijana
AU  - Pavlović, Sonja
AU  - Colović, Milica
PY  - 2012
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/609
AB  - Based on current findings, the presence of NPM1 mutations in acute myeloid leukemia (AML) patients is associated with an increased probability of complete remission (CR) and better overall survival (OS). We determined the incidence and prognostic relevance of NPM1 mutations, their association with FLT3 and IDH mutations, and other clinical characteristics in Serbian adult AML patients. Samples from 111 adult de novo AML patients, including 73 AML cases with a normal karyotype (NK-AML), were studied. NPM1, FLT3, and IDH mutations were detected by PCR and direct sequencing. NPM1 mutations were detected in 22.5% of patients. The presence of NPM1 mutations predicted a low CR rate and shorter OS. NPM1 mutations showed an association with both FLT3 and IDH mutations. Survival analysis based on NPM1/FLT3 mutational status revealed a lower OS for NPM1(+)/FLT3(-) compared to the NPM1(-)/FLT3(-) group in NK-AML patients. The lack of impact or unfavorable prognostic effect of NPM1 mutations found in this study can be assigned to a small cohort of analyzed AML patients, as can the presence of FLT3 and IDH mutations or other genetic lesions that cooperate with NPM1 mutations influencing prognosis.
PB  - Karger, Basel
T2  - Acta Haematologica
T1  - Prognostic Impact of NPM1 Mutations in Serbian Adult Patients with Acute Myeloid Leukemia
EP  - 212
IS  - 4
SP  - 203
VL  - 128
DO  - 10.1159/000339506
ER  - 

@article{
author = "Kuzmanović, Milos and Tošić, Nataša and Čolović, Nataša and Karan-Đurašević, Teodora and Spasovski, Vesna and Ugrin, Milena and Nikčević, Gordana and Suvajdžić-Vuković, Nada and Tomin, Dragica and Vidović, Ana and Virijević, Marijana and Pavlović, Sonja and Colović, Milica",
year = "2012",
abstract = "Based on current findings, the presence of NPM1 mutations in acute myeloid leukemia (AML) patients is associated with an increased probability of complete remission (CR) and better overall survival (OS). We determined the incidence and prognostic relevance of NPM1 mutations, their association with FLT3 and IDH mutations, and other clinical characteristics in Serbian adult AML patients. Samples from 111 adult de novo AML patients, including 73 AML cases with a normal karyotype (NK-AML), were studied. NPM1, FLT3, and IDH mutations were detected by PCR and direct sequencing. NPM1 mutations were detected in 22.5% of patients. The presence of NPM1 mutations predicted a low CR rate and shorter OS. NPM1 mutations showed an association with both FLT3 and IDH mutations. Survival analysis based on NPM1/FLT3 mutational status revealed a lower OS for NPM1(+)/FLT3(-) compared to the NPM1(-)/FLT3(-) group in NK-AML patients. The lack of impact or unfavorable prognostic effect of NPM1 mutations found in this study can be assigned to a small cohort of analyzed AML patients, as can the presence of FLT3 and IDH mutations or other genetic lesions that cooperate with NPM1 mutations influencing prognosis.",
publisher = "Karger, Basel",
journal = "Acta Haematologica",
title = "Prognostic Impact of NPM1 Mutations in Serbian Adult Patients with Acute Myeloid Leukemia",
pages = "212-203",
number = "4",
volume = "128",
doi = "10.1159/000339506"
}

Kuzmanović, M., Tošić, N., Čolović, N., Karan-Đurašević, T., Spasovski, V., Ugrin, M., Nikčević, G., Suvajdžić-Vuković, N., Tomin, D., Vidović, A., Virijević, M., Pavlović, S.,& Colović, M.. (2012). Prognostic Impact of NPM1 Mutations in Serbian Adult Patients with Acute Myeloid Leukemia. in Acta Haematologica
Karger, Basel., 128(4), 203-212.
https://doi.org/10.1159/000339506

Kuzmanović M, Tošić N, Čolović N, Karan-Đurašević T, Spasovski V, Ugrin M, Nikčević G, Suvajdžić-Vuković N, Tomin D, Vidović A, Virijević M, Pavlović S, Colović M. Prognostic Impact of NPM1 Mutations in Serbian Adult Patients with Acute Myeloid Leukemia. in Acta Haematologica. 2012;128(4):203-212.
doi:10.1159/000339506 .

Kuzmanović, Milos, Tošić, Nataša, Čolović, Nataša, Karan-Đurašević, Teodora, Spasovski, Vesna, Ugrin, Milena, Nikčević, Gordana, Suvajdžić-Vuković, Nada, Tomin, Dragica, Vidović, Ana, Virijević, Marijana, Pavlović, Sonja, Colović, Milica, "Prognostic Impact of NPM1 Mutations in Serbian Adult Patients with Acute Myeloid Leukemia" in Acta Haematologica, 128, no. 4 (2012):203-212,
https://doi.org/10.1159/000339506 . .