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

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

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

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

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

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  - Klampfl, Thorsten
AU  - Milosević, Jelena D.
AU  - Puda, Ana
AU  - Schoenegger, Andreas
AU  - Bagienski, Klaudia
AU  - Berg, Tiina
AU  - Harutyunyan, Ashot S.
AU  - Gisslinger, Bettina
AU  - Rumi, Elisa
AU  - Malcovati, Luca
AU  - Pietra, Daniela
AU  - Elena, Chiara
AU  - Della Porta, Matteo Giovanni
AU  - Pieri, Lisa
AU  - Guglielmelli, Paola
AU  - Bock, Christoph
AU  - Doubek, Michael
AU  - Dvorakova, Dana
AU  - Suvajdžić, Nada
AU  - Tomin, Dragica
AU  - Tošić, Nataša
AU  - Racil, Zdenek
AU  - Steurer, Michael
AU  - Pavlović, Sonja
AU  - Vannucchi, Alessandro M.
AU  - Cazzola, Mario
AU  - Gisslinger, Heinz
AU  - Kralovics, Robert
PY  - 2013
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/673
AB  - Exome sequencing of primary tumors identifies complex somatic mutation patterns. Assignment of relevance of individual somatic mutations is difficult and poses the next challenge for interpretation of next generation sequencing data. Here we present an approach how exome sequencing in combination with SNP microarray data may identify targets of chromosomal aberrations in myeloid malignancies. The rationale of this approach is that hotspots of chromosomal aberrations might also harbor point mutations in the target genes of deletions, gains or uniparental disomies (UPDs). Chromosome 11 is a frequent target of lesions in myeloid malignancies. Therefore, we studied chromosome 11 in a total of 813 samples from 773 individual patients with different myeloid malignancies by SNP microarrays and complemented the data with exome sequencing in selected cases exhibiting chromosome 11 defects. We found gains, losses and UPDs of chromosome 11 in 52 of the 813 samples (6.4%). Chromosome 11q UPDs frequently associated with mutations of CBL. In one patient the 11qUPD amplified somatic mutations in both CBL and the DNA repair gene DDB1. A duplication within MLL exon 3 was detected in another patient with 11qUPD. We identified several common deleted regions (CDR) on chromosome 11. One of the CDRs associated with de novo acute myeloid leukemia (P=0.013). One patient with a deletion at the LMO2 locus harbored an additional point mutation on the other allele indicating that LMO2 might be a tumor suppressor frequently targeted by 11p deletions. Our chromosome-centered analysis indicates that chromosome 11 contains a number of tumor suppressor genes and that the role of this chromosome in myeloid malignancies is more complex than previously recognized.
PB  - Public Library Science, San Francisco
T2  - PLoS One
T1  - Complex Patterns of Chromosome 11 Aberrations in Myeloid Malignancies Target CBL, MLL, DDB1 and LMO2
IS  - 10
VL  - 8
DO  - 10.1371/journal.pone.0077819
ER  - 

@article{
author = "Klampfl, Thorsten and Milosević, Jelena D. and Puda, Ana and Schoenegger, Andreas and Bagienski, Klaudia and Berg, Tiina and Harutyunyan, Ashot S. and Gisslinger, Bettina and Rumi, Elisa and Malcovati, Luca and Pietra, Daniela and Elena, Chiara and Della Porta, Matteo Giovanni and Pieri, Lisa and Guglielmelli, Paola and Bock, Christoph and Doubek, Michael and Dvorakova, Dana and Suvajdžić, Nada and Tomin, Dragica and Tošić, Nataša and Racil, Zdenek and Steurer, Michael and Pavlović, Sonja and Vannucchi, Alessandro M. and Cazzola, Mario and Gisslinger, Heinz and Kralovics, Robert",
year = "2013",
abstract = "Exome sequencing of primary tumors identifies complex somatic mutation patterns. Assignment of relevance of individual somatic mutations is difficult and poses the next challenge for interpretation of next generation sequencing data. Here we present an approach how exome sequencing in combination with SNP microarray data may identify targets of chromosomal aberrations in myeloid malignancies. The rationale of this approach is that hotspots of chromosomal aberrations might also harbor point mutations in the target genes of deletions, gains or uniparental disomies (UPDs). Chromosome 11 is a frequent target of lesions in myeloid malignancies. Therefore, we studied chromosome 11 in a total of 813 samples from 773 individual patients with different myeloid malignancies by SNP microarrays and complemented the data with exome sequencing in selected cases exhibiting chromosome 11 defects. We found gains, losses and UPDs of chromosome 11 in 52 of the 813 samples (6.4%). Chromosome 11q UPDs frequently associated with mutations of CBL. In one patient the 11qUPD amplified somatic mutations in both CBL and the DNA repair gene DDB1. A duplication within MLL exon 3 was detected in another patient with 11qUPD. We identified several common deleted regions (CDR) on chromosome 11. One of the CDRs associated with de novo acute myeloid leukemia (P=0.013). One patient with a deletion at the LMO2 locus harbored an additional point mutation on the other allele indicating that LMO2 might be a tumor suppressor frequently targeted by 11p deletions. Our chromosome-centered analysis indicates that chromosome 11 contains a number of tumor suppressor genes and that the role of this chromosome in myeloid malignancies is more complex than previously recognized.",
publisher = "Public Library Science, San Francisco",
journal = "PLoS One",
title = "Complex Patterns of Chromosome 11 Aberrations in Myeloid Malignancies Target CBL, MLL, DDB1 and LMO2",
number = "10",
volume = "8",
doi = "10.1371/journal.pone.0077819"
}

Klampfl, T., Milosević, J. D., Puda, A., Schoenegger, A., Bagienski, K., Berg, T., Harutyunyan, A. S., Gisslinger, B., Rumi, E., Malcovati, L., Pietra, D., Elena, C., Della Porta, M. G., Pieri, L., Guglielmelli, P., Bock, C., Doubek, M., Dvorakova, D., Suvajdžić, N., Tomin, D., Tošić, N., Racil, Z., Steurer, M., Pavlović, S., Vannucchi, A. M., Cazzola, M., Gisslinger, H.,& Kralovics, R.. (2013). Complex Patterns of Chromosome 11 Aberrations in Myeloid Malignancies Target CBL, MLL, DDB1 and LMO2. in PLoS One
Public Library Science, San Francisco., 8(10).
https://doi.org/10.1371/journal.pone.0077819

Klampfl T, Milosević JD, Puda A, Schoenegger A, Bagienski K, Berg T, Harutyunyan AS, Gisslinger B, Rumi E, Malcovati L, Pietra D, Elena C, Della Porta MG, Pieri L, Guglielmelli P, Bock C, Doubek M, Dvorakova D, Suvajdžić N, Tomin D, Tošić N, Racil Z, Steurer M, Pavlović S, Vannucchi AM, Cazzola M, Gisslinger H, Kralovics R. Complex Patterns of Chromosome 11 Aberrations in Myeloid Malignancies Target CBL, MLL, DDB1 and LMO2. in PLoS One. 2013;8(10).
doi:10.1371/journal.pone.0077819 .

Klampfl, Thorsten, Milosević, Jelena D., Puda, Ana, Schoenegger, Andreas, Bagienski, Klaudia, Berg, Tiina, Harutyunyan, Ashot S., Gisslinger, Bettina, Rumi, Elisa, Malcovati, Luca, Pietra, Daniela, Elena, Chiara, Della Porta, Matteo Giovanni, Pieri, Lisa, Guglielmelli, Paola, Bock, Christoph, Doubek, Michael, Dvorakova, Dana, Suvajdžić, Nada, Tomin, Dragica, Tošić, Nataša, Racil, Zdenek, Steurer, Michael, Pavlović, Sonja, Vannucchi, Alessandro M., Cazzola, Mario, Gisslinger, Heinz, Kralovics, Robert, "Complex Patterns of Chromosome 11 Aberrations in Myeloid Malignancies Target CBL, MLL, DDB1 and LMO2" in PLoS One, 8, no. 10 (2013),
https://doi.org/10.1371/journal.pone.0077819 . .

TY  - JOUR
AU  - Milosević, Jelena D.
AU  - Puda, Ana
AU  - Malcovati, Luca
AU  - Berg, Tiina
AU  - Hofbauer, Michael
AU  - Stukalov, Alexey
AU  - Klampfl, Thorsten
AU  - Harutyunyan, Ashot S.
AU  - Gisslinger, Heinz
AU  - Gisslinger, Bettina
AU  - Burjanivova, Tatiana
AU  - Rumi, Elisa
AU  - Pietra, Daniela
AU  - Elena, Chiara
AU  - Vannucchi, Alessandro M.
AU  - Doubek, Michael
AU  - Dvorakova, Dana
AU  - Robesova, Blanka
AU  - Wieser, Rotraud
AU  - Koller, Elisabeth
AU  - Suvajdžić, Nada
AU  - Tomin, Dragica
AU  - Tošić, Nataša
AU  - Colinge, Jacques
AU  - Racil, Zdenek
AU  - Steurer, Michael
AU  - Pavlović, Sonja
AU  - Cazzola, Mario
AU  - Kralovics, Robert
PY  - 2012
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/590
AB  - The study aimed to identify genetic lesions associated with secondary acute myeloid leukemia (sAML) in comparison with AML arising de novo (dnAML) and assess their impact on patients' overall survival (OS). High-resolution genotyping and loss of heterozygosity mapping was performed on DNA samples from 86 sAML and 117 dnAML patients, using Affymetrix Genome-Wide Human SNP 6.0 arrays. Genes TP53, RUNX1, CBL, IDH1/2, NRAS, NPM1, and FLT3 were analyzed for mutations in all patients. We identified 36 recurrent cytogenetic aberrations (more than five events). Mutations in TP53, 9pUPD, and del7q (targeting CUX1 locus) were significantly associated with sAML, while NPM1 and FLT3 mutations associated with dnAML. Patients with sAML carrying TP53 mutations demonstrated lower 1-year OS rate than those with wild-type TP53 (14.3% +/- 9.4% vs. 35.4% +/- 7.2%; P = 0.002), while complex karyotype, del7q (CUX1) and del7p (IKZF1) showed no significant effect on OS. Multivariate analysis confirmed that mutant TP53 was the only independent adverse prognostic factor for OS in sAML (hazard ratio 2.67; 95% CI: 1.335.37; P = 0.006). Patients with dnAML and complex karyotype carried sAML-associated defects (TP53 defects in 54.5%, deletions targeting FOXP1 and ETV6 loci in 45.4% of the cases). We identified several co-occurring lesions associated with either sAML or dnAML diagnosis. Our data suggest that distinct genetic lesions drive leukemogenesis in sAML. High karyotype complexity of sAML patients does not influence OS. Somatic mutations in TP53 are the only independent adverse prognostic factor in sAML. Patients with dnAML and complex karyotype show genetic features associated with sAML and myeloproliferative neoplasms. Am. J. Hematol., 2012.
PB  - Wiley, Hoboken
T2  - American Journal of Hematology
T1  - Clinical significance of genetic aberrations in secondary acute myeloid leukemia
EP  - 1016
IS  - 11
SP  - 1010
VL  - 87
DO  - 10.1002/ajh.23309
ER  - 

@article{
author = "Milosević, Jelena D. and Puda, Ana and Malcovati, Luca and Berg, Tiina and Hofbauer, Michael and Stukalov, Alexey and Klampfl, Thorsten and Harutyunyan, Ashot S. and Gisslinger, Heinz and Gisslinger, Bettina and Burjanivova, Tatiana and Rumi, Elisa and Pietra, Daniela and Elena, Chiara and Vannucchi, Alessandro M. and Doubek, Michael and Dvorakova, Dana and Robesova, Blanka and Wieser, Rotraud and Koller, Elisabeth and Suvajdžić, Nada and Tomin, Dragica and Tošić, Nataša and Colinge, Jacques and Racil, Zdenek and Steurer, Michael and Pavlović, Sonja and Cazzola, Mario and Kralovics, Robert",
year = "2012",
abstract = "The study aimed to identify genetic lesions associated with secondary acute myeloid leukemia (sAML) in comparison with AML arising de novo (dnAML) and assess their impact on patients' overall survival (OS). High-resolution genotyping and loss of heterozygosity mapping was performed on DNA samples from 86 sAML and 117 dnAML patients, using Affymetrix Genome-Wide Human SNP 6.0 arrays. Genes TP53, RUNX1, CBL, IDH1/2, NRAS, NPM1, and FLT3 were analyzed for mutations in all patients. We identified 36 recurrent cytogenetic aberrations (more than five events). Mutations in TP53, 9pUPD, and del7q (targeting CUX1 locus) were significantly associated with sAML, while NPM1 and FLT3 mutations associated with dnAML. Patients with sAML carrying TP53 mutations demonstrated lower 1-year OS rate than those with wild-type TP53 (14.3% +/- 9.4% vs. 35.4% +/- 7.2%; P = 0.002), while complex karyotype, del7q (CUX1) and del7p (IKZF1) showed no significant effect on OS. Multivariate analysis confirmed that mutant TP53 was the only independent adverse prognostic factor for OS in sAML (hazard ratio 2.67; 95% CI: 1.335.37; P = 0.006). Patients with dnAML and complex karyotype carried sAML-associated defects (TP53 defects in 54.5%, deletions targeting FOXP1 and ETV6 loci in 45.4% of the cases). We identified several co-occurring lesions associated with either sAML or dnAML diagnosis. Our data suggest that distinct genetic lesions drive leukemogenesis in sAML. High karyotype complexity of sAML patients does not influence OS. Somatic mutations in TP53 are the only independent adverse prognostic factor in sAML. Patients with dnAML and complex karyotype show genetic features associated with sAML and myeloproliferative neoplasms. Am. J. Hematol., 2012.",
publisher = "Wiley, Hoboken",
journal = "American Journal of Hematology",
title = "Clinical significance of genetic aberrations in secondary acute myeloid leukemia",
pages = "1016-1010",
number = "11",
volume = "87",
doi = "10.1002/ajh.23309"
}

Milosević, J. D., Puda, A., Malcovati, L., Berg, T., Hofbauer, M., Stukalov, A., Klampfl, T., Harutyunyan, A. S., Gisslinger, H., Gisslinger, B., Burjanivova, T., Rumi, E., Pietra, D., Elena, C., Vannucchi, A. M., Doubek, M., Dvorakova, D., Robesova, B., Wieser, R., Koller, E., Suvajdžić, N., Tomin, D., Tošić, N., Colinge, J., Racil, Z., Steurer, M., Pavlović, S., Cazzola, M.,& Kralovics, R.. (2012). Clinical significance of genetic aberrations in secondary acute myeloid leukemia. in American Journal of Hematology
Wiley, Hoboken., 87(11), 1010-1016.
https://doi.org/10.1002/ajh.23309

Milosević JD, Puda A, Malcovati L, Berg T, Hofbauer M, Stukalov A, Klampfl T, Harutyunyan AS, Gisslinger H, Gisslinger B, Burjanivova T, Rumi E, Pietra D, Elena C, Vannucchi AM, Doubek M, Dvorakova D, Robesova B, Wieser R, Koller E, Suvajdžić N, Tomin D, Tošić N, Colinge J, Racil Z, Steurer M, Pavlović S, Cazzola M, Kralovics R. Clinical significance of genetic aberrations in secondary acute myeloid leukemia. in American Journal of Hematology. 2012;87(11):1010-1016.
doi:10.1002/ajh.23309 .

Milosević, Jelena D., Puda, Ana, Malcovati, Luca, Berg, Tiina, Hofbauer, Michael, Stukalov, Alexey, Klampfl, Thorsten, Harutyunyan, Ashot S., Gisslinger, Heinz, Gisslinger, Bettina, Burjanivova, Tatiana, Rumi, Elisa, Pietra, Daniela, Elena, Chiara, Vannucchi, Alessandro M., Doubek, Michael, Dvorakova, Dana, Robesova, Blanka, Wieser, Rotraud, Koller, Elisabeth, Suvajdžić, Nada, Tomin, Dragica, Tošić, Nataša, Colinge, Jacques, Racil, Zdenek, Steurer, Michael, Pavlović, Sonja, Cazzola, Mario, Kralovics, Robert, "Clinical significance of genetic aberrations in secondary acute myeloid leukemia" in American Journal of Hematology, 87, no. 11 (2012):1010-1016,
https://doi.org/10.1002/ajh.23309 . .

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 . .