TY  - CONF
AU  - Virijević, Marijana
AU  - Marjanović, Irena
AU  - Anđelković, Marina
AU  - Vuković, Nada Suvajdžić
AU  - Jaković, Ljubomir
AU  - Micić, Dragan
AU  - Lalosević, Milica Stojković
AU  - Bogdanović, Andrija
AU  - Pavlović, Sonja
PY  - 2023
UR  - https://journals.lww.com/hemasphere/fulltext/2023/08003/pb2037__new_tert_variant_in_a_family_with_aplastic.1913.aspx
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/2156
AB  - Background:TERT gene, the most frequently mutated gene in patients with telomere biology disorders (telomeropathies), encode telomerase reverse transcriptase enzyme. Heterozygous variants in the TERT gene impair telomerase activity by haploinsufficiency and pathogenic variants are associated with bone marrow failure syndrome and acute myeloid leukemia predisposition. TERT variants show incomplete penetrance and can also be found in asymptomatic family members. Some patients with telomeropathies present with severe symptoms at early age, and in other diseases may appear later in life like aplastic anemia, pulmonary or hepatic fibrosis. Affected families may show anticipation that may result in more severe forms of the disease in succeeding generations. Due to the rarity of the disease and the small number of clinical trials, telomeropathies are often unrecognized and misdiagnosed.  Aims: To report a novel variant in TERT gene in familial hematopoietic disorder.  Methods: Next Generation Sequencing of DNA isolated from peripheral blood of a patient (older sister) with clinical diagnosis of aplastic anemia, using TruSight One MiSeq platform (Illumina®) and segregation sequencing analysis of patient’s mother and younger sister.  Results: We analyzed all three family members presented with a similar clinical appearance and hematology findings (moderate megaloblastic pancytopenia). Mother was diagnosed at age 14, but reevaluated before delivery in 2001 as hypoplastic MDS and trisomy 8 in karyotype with marked thrombocytopenia, being stable for years. Two daughters, both diagnosed as familiar aplastic anemia with normal karyotype, without elements of Fanconi anemia, at age of 13 and 14 yrs, also with profound thrombocytopenia without severe bleeding episodes. Moreover, lung and liver fibrosis were excluded. We identified a novel missense heterozygous variant c.2605G>A p.(Asp869Asn) in TERT gene in all three family members. This variant results in replacement of aspartic amino acid on 869 position in TERT enzyme polypeptide chain by asparagine. According to ACMG classification, detected variant is characterized as likely pathogenic, class 2. This variant is very rare and was detected in gnomAD exomes and gnomAD genomes data bases. It is located in highly conserved protein region and is very likely to disrupt the function of the enzyme.  Summary/Conclusion: As patients with telomeropathies often have a history of macrocytosis and mild to moderate thrombocytopenia, that can be wrongly diagnosed as immune-mediated thrombocytopenia, myelodysplastic syndrome or moderate aplastic anemia, our findings indicate that TERT rare variants pass under-recognized in these patients. Therefore, this report emphasizes the importance for routine deep genetics screening for TERT rare variants in patients with family history of cytopenia, different bone marrow failure syndromes and aplastic anemia, regardless the age or clinical presentation. This investigation is able to identify clinically inapparent telomere biology disorder and improve outcomes through forehand diagnosis setting, genetic counseling and the precise therapy considerations especially stem cell grafting.
C3  - HemaSphere
T1  - PB2037: NEW TERT VARIANT IN A FAMILY WITH APLASTIC ANEMIA
IS  - S3
SP  - e62401c5
VL  - 7
DO  - 10.1097/01.HS9.0000974956.62401.c5
ER  - 

@conference{
author = "Virijević, Marijana and Marjanović, Irena and Anđelković, Marina and Vuković, Nada Suvajdžić and Jaković, Ljubomir and Micić, Dragan and Lalosević, Milica Stojković and Bogdanović, Andrija and Pavlović, Sonja",
year = "2023",
abstract = "Background:TERT gene, the most frequently mutated gene in patients with telomere biology disorders (telomeropathies), encode telomerase reverse transcriptase enzyme. Heterozygous variants in the TERT gene impair telomerase activity by haploinsufficiency and pathogenic variants are associated with bone marrow failure syndrome and acute myeloid leukemia predisposition. TERT variants show incomplete penetrance and can also be found in asymptomatic family members. Some patients with telomeropathies present with severe symptoms at early age, and in other diseases may appear later in life like aplastic anemia, pulmonary or hepatic fibrosis. Affected families may show anticipation that may result in more severe forms of the disease in succeeding generations. Due to the rarity of the disease and the small number of clinical trials, telomeropathies are often unrecognized and misdiagnosed.  Aims: To report a novel variant in TERT gene in familial hematopoietic disorder.  Methods: Next Generation Sequencing of DNA isolated from peripheral blood of a patient (older sister) with clinical diagnosis of aplastic anemia, using TruSight One MiSeq platform (Illumina®) and segregation sequencing analysis of patient’s mother and younger sister.  Results: We analyzed all three family members presented with a similar clinical appearance and hematology findings (moderate megaloblastic pancytopenia). Mother was diagnosed at age 14, but reevaluated before delivery in 2001 as hypoplastic MDS and trisomy 8 in karyotype with marked thrombocytopenia, being stable for years. Two daughters, both diagnosed as familiar aplastic anemia with normal karyotype, without elements of Fanconi anemia, at age of 13 and 14 yrs, also with profound thrombocytopenia without severe bleeding episodes. Moreover, lung and liver fibrosis were excluded. We identified a novel missense heterozygous variant c.2605G>A p.(Asp869Asn) in TERT gene in all three family members. This variant results in replacement of aspartic amino acid on 869 position in TERT enzyme polypeptide chain by asparagine. According to ACMG classification, detected variant is characterized as likely pathogenic, class 2. This variant is very rare and was detected in gnomAD exomes and gnomAD genomes data bases. It is located in highly conserved protein region and is very likely to disrupt the function of the enzyme.  Summary/Conclusion: As patients with telomeropathies often have a history of macrocytosis and mild to moderate thrombocytopenia, that can be wrongly diagnosed as immune-mediated thrombocytopenia, myelodysplastic syndrome or moderate aplastic anemia, our findings indicate that TERT rare variants pass under-recognized in these patients. Therefore, this report emphasizes the importance for routine deep genetics screening for TERT rare variants in patients with family history of cytopenia, different bone marrow failure syndromes and aplastic anemia, regardless the age or clinical presentation. This investigation is able to identify clinically inapparent telomere biology disorder and improve outcomes through forehand diagnosis setting, genetic counseling and the precise therapy considerations especially stem cell grafting.",
journal = "HemaSphere",
title = "PB2037: NEW TERT VARIANT IN A FAMILY WITH APLASTIC ANEMIA",
number = "S3",
pages = "e62401c5",
volume = "7",
doi = "10.1097/01.HS9.0000974956.62401.c5"
}

Virijević, M., Marjanović, I., Anđelković, M., Vuković, N. S., Jaković, L., Micić, D., Lalosević, M. S., Bogdanović, A.,& Pavlović, S.. (2023). PB2037: NEW TERT VARIANT IN A FAMILY WITH APLASTIC ANEMIA. in HemaSphere, 7(S3), e62401c5.
https://doi.org/10.1097/01.HS9.0000974956.62401.c5

Virijević M, Marjanović I, Anđelković M, Vuković NS, Jaković L, Micić D, Lalosević MS, Bogdanović A, Pavlović S. PB2037: NEW TERT VARIANT IN A FAMILY WITH APLASTIC ANEMIA. in HemaSphere. 2023;7(S3):e62401c5.
doi:10.1097/01.HS9.0000974956.62401.c5 .

Virijević, Marijana, Marjanović, Irena, Anđelković, Marina, Vuković, Nada Suvajdžić, Jaković, Ljubomir, Micić, Dragan, Lalosević, Milica Stojković, Bogdanović, Andrija, Pavlović, Sonja, "PB2037: NEW TERT VARIANT IN A FAMILY WITH APLASTIC ANEMIA" in HemaSphere, 7, no. S3 (2023):e62401c5,
https://doi.org/10.1097/01.HS9.0000974956.62401.c5 . .

TY  - JOUR
AU  - Jaković, Ljubomir
AU  - Fekete, Marija Dencic
AU  - Virijević, Marijana
AU  - Kraguljac Kurtović, Nada
AU  - Todorić-Zivanović, Biljana
AU  - Stamatović, Dragana
AU  - Karan-Đurašević, Teodora
AU  - Pavlović, Sonja
AU  - Leković, Danijela
AU  - Bogdanović, Andrija
PY  - 2022
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/1592
AB  - De novo AMLs with typical nonrandom chromosomal abnormalities are often associated with specific morphology subtypes. The t(8;21) is one of the most prominent recurrent cytogenetic aberrations (RCA) in AML, frequently associated with AML with maturation, and is characterized as a good prognostic marker. On the contrary, BCR::ABL1 rearrangement is rarely observed in AMLs, without specific morphology, carrying poor prognosis. Its distinction from blastic transformation of chronic myeloid leukemia has been a matter of long debate. The revised WHO classification (2016) recognized AML with BCR::ABL1(+) as a provisional entity. The occurrence of additional cytogenetic aberrations in AML RCA within the same leukemic clone has been detected, albeit rare cases of BCR::ABL1(+) were reported, mainly as subclones. Those additional cytogenetic and molecular findings seem to significantly affect patient prognosis. Conventional cytogenetic analysis, fluorescent in situ hybridization (FISH), and polymerase chain reaction (PCR) were applied at presentation and during the follow-up of the patient. We present a 34-year-old male patient with de novo AML harboring concomitant t(8;21) and t(9;22) in a single clone. The presence of both t(8;21) and Philadelphia chromosome (Ph+) in the same metaphases but in less than 100% of the analyzed cells, the p190 BCR::ABL transcript type, and absence of splenomegaly support that additional BCR::ABL1(+) is a part of the main leukemic clone. These findings, accompanied with an encouraging outcome of continuous cytogenetic and molecular remission after induction therapy, support BCR::ABL1 being a secondary genetic event in AML with t(8;21).
PB  - Heidelberg : Springer
T2  - Journal of Hematopathology
T1  - De novo acute myeloid leukemia harboring concomitant t(8;21)(q22;q22);RUNX1::RUNX1T1 and BCR::ABL1 (p190 minor transcript)
EP  - 195
IS  - 3
SP  - 191
VL  - 15
DO  - 10.1007/s12308-022-00509-4
ER  - 

@article{
author = "Jaković, Ljubomir and Fekete, Marija Dencic and Virijević, Marijana and Kraguljac Kurtović, Nada and Todorić-Zivanović, Biljana and Stamatović, Dragana and Karan-Đurašević, Teodora and Pavlović, Sonja and Leković, Danijela and Bogdanović, Andrija",
year = "2022",
abstract = "De novo AMLs with typical nonrandom chromosomal abnormalities are often associated with specific morphology subtypes. The t(8;21) is one of the most prominent recurrent cytogenetic aberrations (RCA) in AML, frequently associated with AML with maturation, and is characterized as a good prognostic marker. On the contrary, BCR::ABL1 rearrangement is rarely observed in AMLs, without specific morphology, carrying poor prognosis. Its distinction from blastic transformation of chronic myeloid leukemia has been a matter of long debate. The revised WHO classification (2016) recognized AML with BCR::ABL1(+) as a provisional entity. The occurrence of additional cytogenetic aberrations in AML RCA within the same leukemic clone has been detected, albeit rare cases of BCR::ABL1(+) were reported, mainly as subclones. Those additional cytogenetic and molecular findings seem to significantly affect patient prognosis. Conventional cytogenetic analysis, fluorescent in situ hybridization (FISH), and polymerase chain reaction (PCR) were applied at presentation and during the follow-up of the patient. We present a 34-year-old male patient with de novo AML harboring concomitant t(8;21) and t(9;22) in a single clone. The presence of both t(8;21) and Philadelphia chromosome (Ph+) in the same metaphases but in less than 100% of the analyzed cells, the p190 BCR::ABL transcript type, and absence of splenomegaly support that additional BCR::ABL1(+) is a part of the main leukemic clone. These findings, accompanied with an encouraging outcome of continuous cytogenetic and molecular remission after induction therapy, support BCR::ABL1 being a secondary genetic event in AML with t(8;21).",
publisher = "Heidelberg : Springer",
journal = "Journal of Hematopathology",
title = "De novo acute myeloid leukemia harboring concomitant t(8;21)(q22;q22);RUNX1::RUNX1T1 and BCR::ABL1 (p190 minor transcript)",
pages = "195-191",
number = "3",
volume = "15",
doi = "10.1007/s12308-022-00509-4"
}

Jaković, L., Fekete, M. D., Virijević, M., Kraguljac Kurtović, N., Todorić-Zivanović, B., Stamatović, D., Karan-Đurašević, T., Pavlović, S., Leković, D.,& Bogdanović, A.. (2022). De novo acute myeloid leukemia harboring concomitant t(8;21)(q22;q22);RUNX1::RUNX1T1 and BCR::ABL1 (p190 minor transcript). in Journal of Hematopathology
Heidelberg : Springer., 15(3), 191-195.
https://doi.org/10.1007/s12308-022-00509-4

Jaković L, Fekete MD, Virijević M, Kraguljac Kurtović N, Todorić-Zivanović B, Stamatović D, Karan-Đurašević T, Pavlović S, Leković D, Bogdanović A. De novo acute myeloid leukemia harboring concomitant t(8;21)(q22;q22);RUNX1::RUNX1T1 and BCR::ABL1 (p190 minor transcript). in Journal of Hematopathology. 2022;15(3):191-195.
doi:10.1007/s12308-022-00509-4 .

Jaković, Ljubomir, Fekete, Marija Dencic, Virijević, Marijana, Kraguljac Kurtović, Nada, Todorić-Zivanović, Biljana, Stamatović, Dragana, Karan-Đurašević, Teodora, Pavlović, Sonja, Leković, Danijela, Bogdanović, Andrija, "De novo acute myeloid leukemia harboring concomitant t(8;21)(q22;q22);RUNX1::RUNX1T1 and BCR::ABL1 (p190 minor transcript)" in Journal of Hematopathology, 15, no. 3 (2022):191-195,
https://doi.org/10.1007/s12308-022-00509-4 . .

TY  - JOUR
AU  - Marjanović, Irena
AU  - Karan-Đurašević, Teodora
AU  - Kostić, Tatjana
AU  - Virijević, Marijana
AU  - Suvajdžić-Vuković, Nada
AU  - Pavlović, Sonja
AU  - Tošić, Nataša
PY  - 2021
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/1506
AB  - Introduction Acute myeloid leukemia with normal karyotype (AML-NK) is the largest group of AML patients with very heterogeneous disease outcome. In order to ensure more precise risk stratification new molecular markers have been introduced, like expression level for BAALC (Brain and Acute Leukemia, Cytoplasmic) and MN1 (Meningioma 1) genes. Methods In this study, we investigated expression level of both genes in 111 adult AML-NK at diagnosis and examined their prognostic potential. Results BAALC and MN1 expression were detected in about one third of the patients, and positive correlation between these two genes was found. The BAALC(+)/or MN1(+) status was not associated with the presence of FLT3-ITD mutations, but exhibited strong correlation with NPM1(wt) status (P  lt  .001). Therefore, among BAALC(+)/or MN1(+) patients the most frequent ones were FLT3-ITD-/NPM1(-) double negative patients with intermediate prognosis. When BAALC(+)/or MN1(+) patients were divided into BAALC(high)/BAALC(low) (21/21) and MN1(high)/MN1(low) (21/22) groups, we detected that BAALC(high)/or MN1(high) patients had a tendency toward lower complete remission rate. Also, survival analysis showed that BAALC(high)/or MN1(high) patients had shorter disease-free survival and overall survival (OS). The most pronounced influence on prognosis was detected in FLT3-ITD-/NPM1(-) group of patients that are lacking reliable prognostic markers, where OS in BAALC(high)/or MN1(high) was only 5 months vs 25 months in BAALC(low)/or MN1(low). Conclusion These findings indicate that BAALC and MN1 expression level could be used for more precise risk stratification of AML-NK patients and especially FLT3-ITD-/NPM1(-) patients, transforming this intermediate-risk group, into a group with an adverse prognosis.
PB  - Wiley, Hoboken
T2  - International Journal of Laboratory Hematology
T1  - Prognostic significance of combined BAALC and MN1 gene expression level in acute myeloid leukemia with normal karyotype
EP  - 440
IS  - 3
SP  - 433
VL  - 43
DO  - 10.1111/ijlh.13405
ER  - 

@article{
author = "Marjanović, Irena and Karan-Đurašević, Teodora and Kostić, Tatjana and Virijević, Marijana and Suvajdžić-Vuković, Nada and Pavlović, Sonja and Tošić, Nataša",
year = "2021",
abstract = "Introduction Acute myeloid leukemia with normal karyotype (AML-NK) is the largest group of AML patients with very heterogeneous disease outcome. In order to ensure more precise risk stratification new molecular markers have been introduced, like expression level for BAALC (Brain and Acute Leukemia, Cytoplasmic) and MN1 (Meningioma 1) genes. Methods In this study, we investigated expression level of both genes in 111 adult AML-NK at diagnosis and examined their prognostic potential. Results BAALC and MN1 expression were detected in about one third of the patients, and positive correlation between these two genes was found. The BAALC(+)/or MN1(+) status was not associated with the presence of FLT3-ITD mutations, but exhibited strong correlation with NPM1(wt) status (P  lt  .001). Therefore, among BAALC(+)/or MN1(+) patients the most frequent ones were FLT3-ITD-/NPM1(-) double negative patients with intermediate prognosis. When BAALC(+)/or MN1(+) patients were divided into BAALC(high)/BAALC(low) (21/21) and MN1(high)/MN1(low) (21/22) groups, we detected that BAALC(high)/or MN1(high) patients had a tendency toward lower complete remission rate. Also, survival analysis showed that BAALC(high)/or MN1(high) patients had shorter disease-free survival and overall survival (OS). The most pronounced influence on prognosis was detected in FLT3-ITD-/NPM1(-) group of patients that are lacking reliable prognostic markers, where OS in BAALC(high)/or MN1(high) was only 5 months vs 25 months in BAALC(low)/or MN1(low). Conclusion These findings indicate that BAALC and MN1 expression level could be used for more precise risk stratification of AML-NK patients and especially FLT3-ITD-/NPM1(-) patients, transforming this intermediate-risk group, into a group with an adverse prognosis.",
publisher = "Wiley, Hoboken",
journal = "International Journal of Laboratory Hematology",
title = "Prognostic significance of combined BAALC and MN1 gene expression level in acute myeloid leukemia with normal karyotype",
pages = "440-433",
number = "3",
volume = "43",
doi = "10.1111/ijlh.13405"
}

Marjanović, I., Karan-Đurašević, T., Kostić, T., Virijević, M., Suvajdžić-Vuković, N., Pavlović, S.,& Tošić, N.. (2021). Prognostic significance of combined BAALC and MN1 gene expression level in acute myeloid leukemia with normal karyotype. in International Journal of Laboratory Hematology
Wiley, Hoboken., 43(3), 433-440.
https://doi.org/10.1111/ijlh.13405

Marjanović I, Karan-Đurašević T, Kostić T, Virijević M, Suvajdžić-Vuković N, Pavlović S, Tošić N. Prognostic significance of combined BAALC and MN1 gene expression level in acute myeloid leukemia with normal karyotype. in International Journal of Laboratory Hematology. 2021;43(3):433-440.
doi:10.1111/ijlh.13405 .

Marjanović, Irena, Karan-Đurašević, Teodora, Kostić, Tatjana, Virijević, Marijana, Suvajdžić-Vuković, Nada, Pavlović, Sonja, Tošić, Nataša, "Prognostic significance of combined BAALC and MN1 gene expression level in acute myeloid leukemia with normal karyotype" in International Journal of Laboratory Hematology, 43, no. 3 (2021):433-440,
https://doi.org/10.1111/ijlh.13405 . .

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  - Kostić, Tatjana
AU  - Virijević, Marijana
AU  - Suvajdžić-Vuković, Nada
AU  - Pavlović, Sonja
AU  - Tošić, Nataša
PY  - 2020
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/1391
AB  - According to current criteria, patients with acute myeloid leukemia with normal karyotype (AML-NK) are classified as intermediate risk patients. There is a constant need for additional molecular markers that will help in substratification into more precise prognostic groups. One of the potential new markers is Ecotropic viral integration 1 site (EVI1) transcriptional factor, whose expression is dissregulated in abnormal hematopoietic process. The purpose of this study was to examine EVI1 gene expression in 104 adult AML-NK patients and on 10 healthy bone marrow donors using real-time polymerase chain reaction method, and to evaluate association between EVI1 expression level and other molecular and clinical features, and to examine its potential influence on the prognosis of the disease. Overexpression of EVI1 gene (EVI1(+) status) was present in 17% of patients. Increased EVI1 expression was predominantly found in patients with lower WBC count (P = 0.003) and lower bone marrow blast percentage (P = 0.005). EVI1(+) patients had lower WT1 expression level (P = 0.041), and were negative for FLT3-ITD and NPM1 mutations (P = 0.036 and P = 0.003). Patients with EVI1(+) status had higher complete remission rate (P = 0.047), but EVI1 expression didn't influence overall and disease free survival. EVI1 expression status alone, cannot be used as a new marker for more precise substratification of AML-NK patients. Further investigations conducted on larger number of patients may indicate how EVI1 expression could influence the prognosis and outcome of AML-NK patients, by itself, or in the context of other molecular and clinical parameters.
PB  - Springer India, New Delhi
T2  - Indian Journal of Hematology and Blood Transfusion
T1  - Expression Pattern and Prognostic Significance of EVI1 Gene in Adult Acute Myeloid Leukemia Patients with Normal Karyotype
EP  - 299
IS  - 2
SP  - 292
VL  - 36
DO  - 10.1007/s12288-019-01227-1
ER  - 

@article{
author = "Marjanović, Irena and Karan-Đurašević, Teodora and Kostić, Tatjana and Virijević, Marijana and Suvajdžić-Vuković, Nada and Pavlović, Sonja and Tošić, Nataša",
year = "2020",
abstract = "According to current criteria, patients with acute myeloid leukemia with normal karyotype (AML-NK) are classified as intermediate risk patients. There is a constant need for additional molecular markers that will help in substratification into more precise prognostic groups. One of the potential new markers is Ecotropic viral integration 1 site (EVI1) transcriptional factor, whose expression is dissregulated in abnormal hematopoietic process. The purpose of this study was to examine EVI1 gene expression in 104 adult AML-NK patients and on 10 healthy bone marrow donors using real-time polymerase chain reaction method, and to evaluate association between EVI1 expression level and other molecular and clinical features, and to examine its potential influence on the prognosis of the disease. Overexpression of EVI1 gene (EVI1(+) status) was present in 17% of patients. Increased EVI1 expression was predominantly found in patients with lower WBC count (P = 0.003) and lower bone marrow blast percentage (P = 0.005). EVI1(+) patients had lower WT1 expression level (P = 0.041), and were negative for FLT3-ITD and NPM1 mutations (P = 0.036 and P = 0.003). Patients with EVI1(+) status had higher complete remission rate (P = 0.047), but EVI1 expression didn't influence overall and disease free survival. EVI1 expression status alone, cannot be used as a new marker for more precise substratification of AML-NK patients. Further investigations conducted on larger number of patients may indicate how EVI1 expression could influence the prognosis and outcome of AML-NK patients, by itself, or in the context of other molecular and clinical parameters.",
publisher = "Springer India, New Delhi",
journal = "Indian Journal of Hematology and Blood Transfusion",
title = "Expression Pattern and Prognostic Significance of EVI1 Gene in Adult Acute Myeloid Leukemia Patients with Normal Karyotype",
pages = "299-292",
number = "2",
volume = "36",
doi = "10.1007/s12288-019-01227-1"
}

Marjanović, I., Karan-Đurašević, T., Kostić, T., Virijević, M., Suvajdžić-Vuković, N., Pavlović, S.,& Tošić, N.. (2020). Expression Pattern and Prognostic Significance of EVI1 Gene in Adult Acute Myeloid Leukemia Patients with Normal Karyotype. in Indian Journal of Hematology and Blood Transfusion
Springer India, New Delhi., 36(2), 292-299.
https://doi.org/10.1007/s12288-019-01227-1

Marjanović I, Karan-Đurašević T, Kostić T, Virijević M, Suvajdžić-Vuković N, Pavlović S, Tošić N. Expression Pattern and Prognostic Significance of EVI1 Gene in Adult Acute Myeloid Leukemia Patients with Normal Karyotype. in Indian Journal of Hematology and Blood Transfusion. 2020;36(2):292-299.
doi:10.1007/s12288-019-01227-1 .

Marjanović, Irena, Karan-Đurašević, Teodora, Kostić, Tatjana, Virijević, Marijana, Suvajdžić-Vuković, Nada, Pavlović, Sonja, Tošić, Nataša, "Expression Pattern and Prognostic Significance of EVI1 Gene in Adult Acute Myeloid Leukemia Patients with Normal Karyotype" in Indian Journal of Hematology and Blood Transfusion, 36, no. 2 (2020):292-299,
https://doi.org/10.1007/s12288-019-01227-1 . .

TY  - JOUR
AU  - Đorđević, Vesna
AU  - Tošić, Nataša
AU  - Denčić-Fekete, Marija
AU  - Virijević, Marijana
AU  - Jovanović, Jelica
AU  - Jaković, Ljubomir
AU  - Kraguljac-Kurtović, Nada
AU  - Bogdanović, Andrija
AU  - Kostić, Tatjana
AU  - Pavlović, Sonja
PY  - 2020
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/1371
AB  - Uvod. Precizno dijagnostikovanje akutne promijelocitne leukemije (APL), ne samo na osnovu morfoloških i kliničkih parametara, već i na molekularnom nivou, veoma je važno radi primene adekvatne ciljane terapije. Prikaz bolesnika. Prikazali smo bolesnicu, staru 62 godine, sa dijagnozom APL. Primenom standardne citogenetičke analize, kao i primenom fluorescentne in situ hibridizacije (FISH), nije bilo potvrđeno prisustvo t(15;17) kod opisane bolesnice. Primenom metode reverzna transkriptazalančana reakcija polimeraze (RT-PCR), identifikovana su dva atipična promyelotic leukemia/retinoic acid receptor alpha (PML/RAR-α) fuziona transkripta. Oba transkripta su predstavljala izoforme. Duži transkript je zadržao "okvir čitanja" i kodirao je funkcionalan PML/RAR-α aberantni protein, dok je kraći transkript bio van "okvira čitanja". Zaključak. Naša studija ukazuje na potrebu za primenom molekularne metodologije u svakodnevnoj kliničkoj praksi. Precizna karakterizacija PML/RAR-α fuzionih transkipta čini osnovu za identifikovanje retkih bolesnika čije lečenje zahteva dodatni oprez. Prema našim saznanjima, ovo je tek peti slučaj opisanog atipičnog PML/RAR-α transkripta koji u sebi sadrži celokupan PML egzon 7a, a među njima jedini koji se nije mogao detektovati primenom citogenetičke i FISH analize. Svi ovde predstavljeni slučajevi su imali smrtni ishod. Zbog toga, naši rezulatati, zajedno sa sličnim slučajevima opisanim u literaturi, naglašavaju značaj detaljne identifikacije atipičnih PML/RAR-α fuzija, ne samo u svrhu prepoznavanja njihove uloge u procesu leukemogeneze, veći i u smislu procene njihovog uticaja na ishod lečenja.
AB  - Introduction. The accurate diagnosis of acute promyelocytic leukemia (APL), not only on the morphological and clinical, but also on the molecular level, is very important for application of targeted therapies. Case report. A 62year-old woman presented with APL. By using conventional cytogenetic analysis as well as applying the fluorescence in situ hybridization (FISH) analysis it has not been possible to confirm the presence of t(15;17) in the presented patient. Using reverse transcriptase polymerase chain reaction (RT-PCR) two atypical promyelotic leukemia/retinoic acid receptor alpha (PML/RAR-α) fusion transcripts were identified. Both detected transcripts were isoforms. The larger transcript was in-frame, coding for functional aberrant PML/RAR-α protein, while the shorter transcript was an out-of-frame. Conclusion. Our study highlights the need for the application of molecular methodology in daily clinical practice. Precise characterization of PML/RAR-α fusion transcript creates a basis for identifying rare individual cases that require special caution when treating such patients. To our knowledge this is only the fifth case of atypical PML/RAR-α transcript containing full PML exon 7a, and among them the only one that was cytogenetically cryptic and FISH negative. All of the herein presented cases had lethal outcome. Therefore, our findings with the additional review of the literature, emphasizes the importance of detailed identification of atypical PML/RAR-α fusions, not only for the purpose of knowing their role in leukemogenesis, but also for the assessment of the impact that they can have on the outcome of the treatment.
PB  - Vojnomedicinska akademija - Institut za naučne informacije, Beograd
T2  - Vojnosanitetski pregled
T1  - Akutna promijelocitna leukemija bez t(15;17) - molekularni dokazi atipične PML/RAR-α transkripcione varijante genskim sekvenciranjem
T1  - Acute promyelocytic leukemia lacking t(15;17): Molecular evidence of atypical PML/RAR-α transcriptional variant by gene sequencing
EP  - 102
IS  - 1
SP  - 97
VL  - 77
DO  - 10.2298/VSP170620040D
ER  - 

@article{
author = "Đorđević, Vesna and Tošić, Nataša and Denčić-Fekete, Marija and Virijević, Marijana and Jovanović, Jelica and Jaković, Ljubomir and Kraguljac-Kurtović, Nada and Bogdanović, Andrija and Kostić, Tatjana and Pavlović, Sonja",
year = "2020",
abstract = "Uvod. Precizno dijagnostikovanje akutne promijelocitne leukemije (APL), ne samo na osnovu morfoloških i kliničkih parametara, već i na molekularnom nivou, veoma je važno radi primene adekvatne ciljane terapije. Prikaz bolesnika. Prikazali smo bolesnicu, staru 62 godine, sa dijagnozom APL. Primenom standardne citogenetičke analize, kao i primenom fluorescentne in situ hibridizacije (FISH), nije bilo potvrđeno prisustvo t(15;17) kod opisane bolesnice. Primenom metode reverzna transkriptazalančana reakcija polimeraze (RT-PCR), identifikovana su dva atipična promyelotic leukemia/retinoic acid receptor alpha (PML/RAR-α) fuziona transkripta. Oba transkripta su predstavljala izoforme. Duži transkript je zadržao "okvir čitanja" i kodirao je funkcionalan PML/RAR-α aberantni protein, dok je kraći transkript bio van "okvira čitanja". Zaključak. Naša studija ukazuje na potrebu za primenom molekularne metodologije u svakodnevnoj kliničkoj praksi. Precizna karakterizacija PML/RAR-α fuzionih transkipta čini osnovu za identifikovanje retkih bolesnika čije lečenje zahteva dodatni oprez. Prema našim saznanjima, ovo je tek peti slučaj opisanog atipičnog PML/RAR-α transkripta koji u sebi sadrži celokupan PML egzon 7a, a među njima jedini koji se nije mogao detektovati primenom citogenetičke i FISH analize. Svi ovde predstavljeni slučajevi su imali smrtni ishod. Zbog toga, naši rezulatati, zajedno sa sličnim slučajevima opisanim u literaturi, naglašavaju značaj detaljne identifikacije atipičnih PML/RAR-α fuzija, ne samo u svrhu prepoznavanja njihove uloge u procesu leukemogeneze, veći i u smislu procene njihovog uticaja na ishod lečenja., Introduction. The accurate diagnosis of acute promyelocytic leukemia (APL), not only on the morphological and clinical, but also on the molecular level, is very important for application of targeted therapies. Case report. A 62year-old woman presented with APL. By using conventional cytogenetic analysis as well as applying the fluorescence in situ hybridization (FISH) analysis it has not been possible to confirm the presence of t(15;17) in the presented patient. Using reverse transcriptase polymerase chain reaction (RT-PCR) two atypical promyelotic leukemia/retinoic acid receptor alpha (PML/RAR-α) fusion transcripts were identified. Both detected transcripts were isoforms. The larger transcript was in-frame, coding for functional aberrant PML/RAR-α protein, while the shorter transcript was an out-of-frame. Conclusion. Our study highlights the need for the application of molecular methodology in daily clinical practice. Precise characterization of PML/RAR-α fusion transcript creates a basis for identifying rare individual cases that require special caution when treating such patients. To our knowledge this is only the fifth case of atypical PML/RAR-α transcript containing full PML exon 7a, and among them the only one that was cytogenetically cryptic and FISH negative. All of the herein presented cases had lethal outcome. Therefore, our findings with the additional review of the literature, emphasizes the importance of detailed identification of atypical PML/RAR-α fusions, not only for the purpose of knowing their role in leukemogenesis, but also for the assessment of the impact that they can have on the outcome of the treatment.",
publisher = "Vojnomedicinska akademija - Institut za naučne informacije, Beograd",
journal = "Vojnosanitetski pregled",
title = "Akutna promijelocitna leukemija bez t(15;17) - molekularni dokazi atipične PML/RAR-α transkripcione varijante genskim sekvenciranjem, Acute promyelocytic leukemia lacking t(15;17): Molecular evidence of atypical PML/RAR-α transcriptional variant by gene sequencing",
pages = "102-97",
number = "1",
volume = "77",
doi = "10.2298/VSP170620040D"
}

Đorđević, V., Tošić, N., Denčić-Fekete, M., Virijević, M., Jovanović, J., Jaković, L., Kraguljac-Kurtović, N., Bogdanović, A., Kostić, T.,& Pavlović, S.. (2020). Akutna promijelocitna leukemija bez t(15;17) - molekularni dokazi atipične PML/RAR-α transkripcione varijante genskim sekvenciranjem. in Vojnosanitetski pregled
Vojnomedicinska akademija - Institut za naučne informacije, Beograd., 77(1), 97-102.
https://doi.org/10.2298/VSP170620040D

Đorđević V, Tošić N, Denčić-Fekete M, Virijević M, Jovanović J, Jaković L, Kraguljac-Kurtović N, Bogdanović A, Kostić T, Pavlović S. Akutna promijelocitna leukemija bez t(15;17) - molekularni dokazi atipične PML/RAR-α transkripcione varijante genskim sekvenciranjem. in Vojnosanitetski pregled. 2020;77(1):97-102.
doi:10.2298/VSP170620040D .

Đorđević, Vesna, Tošić, Nataša, Denčić-Fekete, Marija, Virijević, Marijana, Jovanović, Jelica, Jaković, Ljubomir, Kraguljac-Kurtović, Nada, Bogdanović, Andrija, Kostić, Tatjana, Pavlović, Sonja, "Akutna promijelocitna leukemija bez t(15;17) - molekularni dokazi atipične PML/RAR-α transkripcione varijante genskim sekvenciranjem" in Vojnosanitetski pregled, 77, no. 1 (2020):97-102,
https://doi.org/10.2298/VSP170620040D . .

TY  - JOUR
AU  - Mitrović, Mirjana
AU  - Kostić, Tatjana
AU  - Virijević, Marijana
AU  - Karan-Đurašević, Teodora
AU  - Suvajdžić-Vuković, Nada
AU  - Pavlović, Sonja
AU  - Tošić, Nataša
PY  - 2020
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/1403
AB  - Introduction Patients with acute promyelocytic leukemia (APL) are characterized by the highest expression of Wilms' tumor 1 (WT1) gene compared with other subtypes of acute myeloid leukemia, and yet this molecular marker is almost never used for risk stratification and in therapy response monitoring. Methods Quantitative assessment of Wilms' tumor 1 (WT1) gene transcripts was performed using real-time PCR method. The bone marrow samples were collected at the time of diagnosis for 47 APL patients, and for 31/47 patients during follow-up/relapse of the disease (129 samples in total). We examined how this molecular marker can be used for prognosis and minimal residual disease (MRD) monitoring. Results Increased WT1 expression was found in 34% of patients. WT1(high) status was an independent unfavorable factor for early death occurrence and was associated with shorter overall survival (OS). Assessment of log reduction value of WT1 expression in paired diagnosis/complete remission samples did not reveal its impact on relapse rate, disease-free survival, and OS. Also, measurement of WT1 expression level at different time points during therapy was not a reliable method for MRD monitoring. Conclusion Increased expression of WT1 gene detected in high proportion of APL patients could be considered as a marker for more precise risk stratification models in an attempt to further improve treatment and outcome of APL patients.
PB  - Wiley, Hoboken
T2  - International Journal of Laboratory Hematology
T1  - The influence of Wilms' tumor 1 gene expression level on prognosis and risk stratification of acute promyelocytic leukemia patients
EP  - 87
IS  - 1
SP  - 82
VL  - 42
DO  - 10.1111/ijlh.13144
ER  - 

@article{
author = "Mitrović, Mirjana and Kostić, Tatjana and Virijević, Marijana and Karan-Đurašević, Teodora and Suvajdžić-Vuković, Nada and Pavlović, Sonja and Tošić, Nataša",
year = "2020",
abstract = "Introduction Patients with acute promyelocytic leukemia (APL) are characterized by the highest expression of Wilms' tumor 1 (WT1) gene compared with other subtypes of acute myeloid leukemia, and yet this molecular marker is almost never used for risk stratification and in therapy response monitoring. Methods Quantitative assessment of Wilms' tumor 1 (WT1) gene transcripts was performed using real-time PCR method. The bone marrow samples were collected at the time of diagnosis for 47 APL patients, and for 31/47 patients during follow-up/relapse of the disease (129 samples in total). We examined how this molecular marker can be used for prognosis and minimal residual disease (MRD) monitoring. Results Increased WT1 expression was found in 34% of patients. WT1(high) status was an independent unfavorable factor for early death occurrence and was associated with shorter overall survival (OS). Assessment of log reduction value of WT1 expression in paired diagnosis/complete remission samples did not reveal its impact on relapse rate, disease-free survival, and OS. Also, measurement of WT1 expression level at different time points during therapy was not a reliable method for MRD monitoring. Conclusion Increased expression of WT1 gene detected in high proportion of APL patients could be considered as a marker for more precise risk stratification models in an attempt to further improve treatment and outcome of APL patients.",
publisher = "Wiley, Hoboken",
journal = "International Journal of Laboratory Hematology",
title = "The influence of Wilms' tumor 1 gene expression level on prognosis and risk stratification of acute promyelocytic leukemia patients",
pages = "87-82",
number = "1",
volume = "42",
doi = "10.1111/ijlh.13144"
}

Mitrović, M., Kostić, T., Virijević, M., Karan-Đurašević, T., Suvajdžić-Vuković, N., Pavlović, S.,& Tošić, N.. (2020). The influence of Wilms' tumor 1 gene expression level on prognosis and risk stratification of acute promyelocytic leukemia patients. in International Journal of Laboratory Hematology
Wiley, Hoboken., 42(1), 82-87.
https://doi.org/10.1111/ijlh.13144

Mitrović M, Kostić T, Virijević M, Karan-Đurašević T, Suvajdžić-Vuković N, Pavlović S, Tošić N. The influence of Wilms' tumor 1 gene expression level on prognosis and risk stratification of acute promyelocytic leukemia patients. in International Journal of Laboratory Hematology. 2020;42(1):82-87.
doi:10.1111/ijlh.13144 .

Mitrović, Mirjana, Kostić, Tatjana, Virijević, Marijana, Karan-Đurašević, Teodora, Suvajdžić-Vuković, Nada, Pavlović, Sonja, Tošić, Nataša, "The influence of Wilms' tumor 1 gene expression level on prognosis and risk stratification of acute promyelocytic leukemia patients" in International Journal of Laboratory Hematology, 42, no. 1 (2020):82-87,
https://doi.org/10.1111/ijlh.13144 . .

TY  - CONF
AU  - Fekete, Marija Dencic
AU  - Jaković, Ljubomir
AU  - Virijević, Marijana
AU  - Jovanović, Jelica
AU  - Todorić-Zivanović, Biljana
AU  - Karan-Đurašević, Teodora
AU  - Kraguljac-Kurtović, Nada
AU  - Pavlović, Sonja
AU  - Bogdanović, Andrija
PY  - 2019
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/1249
PB  - BMC, London
C3  - Molecular Cytogenetics
T1  - P1143-De novo acute myeloid leukemia with BCR ABL1 accompanied by t(8;21)(q22;q22.1) RUNX1 RUNX1T1 a rare association
VL  - 12
UR  - https://hdl.handle.net/21.15107/rcub_imagine_1249
ER  - 

@conference{
author = "Fekete, Marija Dencic and Jaković, Ljubomir and Virijević, Marijana and Jovanović, Jelica and Todorić-Zivanović, Biljana and Karan-Đurašević, Teodora and Kraguljac-Kurtović, Nada and Pavlović, Sonja and Bogdanović, Andrija",
year = "2019",
publisher = "BMC, London",
journal = "Molecular Cytogenetics",
title = "P1143-De novo acute myeloid leukemia with BCR ABL1 accompanied by t(8;21)(q22;q22.1) RUNX1 RUNX1T1 a rare association",
volume = "12",
url = "https://hdl.handle.net/21.15107/rcub_imagine_1249"
}

Fekete, M. D., Jaković, L., Virijević, M., Jovanović, J., Todorić-Zivanović, B., Karan-Đurašević, T., Kraguljac-Kurtović, N., Pavlović, S.,& Bogdanović, A.. (2019). P1143-De novo acute myeloid leukemia with BCR ABL1 accompanied by t(8;21)(q22;q22.1) RUNX1 RUNX1T1 a rare association. in Molecular Cytogenetics
BMC, London., 12.
https://hdl.handle.net/21.15107/rcub_imagine_1249

Fekete MD, Jaković L, Virijević M, Jovanović J, Todorić-Zivanović B, Karan-Đurašević T, Kraguljac-Kurtović N, Pavlović S, Bogdanović A. P1143-De novo acute myeloid leukemia with BCR ABL1 accompanied by t(8;21)(q22;q22.1) RUNX1 RUNX1T1 a rare association. in Molecular Cytogenetics. 2019;12.
https://hdl.handle.net/21.15107/rcub_imagine_1249 .

Fekete, Marija Dencic, Jaković, Ljubomir, Virijević, Marijana, Jovanović, Jelica, Todorić-Zivanović, Biljana, Karan-Đurašević, Teodora, Kraguljac-Kurtović, Nada, Pavlović, Sonja, Bogdanović, Andrija, "P1143-De novo acute myeloid leukemia with BCR ABL1 accompanied by t(8;21)(q22;q22.1) RUNX1 RUNX1T1 a rare association" in Molecular Cytogenetics, 12 (2019),
https://hdl.handle.net/21.15107/rcub_imagine_1249 .

TY  - JOUR
AU  - Tošić, Nataša
AU  - Petrović, Isidora
AU  - Kovačević Grujičić, Nataša
AU  - Davidović, Slobodan
AU  - Virijević, Marijana
AU  - Suvajdžić-Vuković, Nada
AU  - Pavlović, Sonja
AU  - Stevanović, Milena
PY  - 2018
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/1196
AB  - Aberrant expression of different SOX (SRY-related high mobility group (HMG) box) genes has been observed in number of tumors but, little is known about their expression patterns in hematological malignancies, especially in acute myeloid leukemia (AML). In this study we investigated SOX2, SOX3, SOX11, SOX14 and SOX18 gene expression in 50 de novo adult AML patients and correlated our findings with known clinical and molecular prognostic markers of the disease. We have found that these genes are overexpressed in 10-22% of patients and preliminary findings suggest that high expression level of these genes may have prognostic significance in AML patients. This is the first study focused on examining the expression level of SOX2, SOX3, SOX11, SOX14 and SOX18 genes in AML patients. Although this is a relatively limited study, initial findings indicate the need for further investigation of these genes, their potential roles in leukemia pathogenesis as well as prognosis in AML patients.
PB  - Pergamon-Elsevier Science Ltd, Oxford
T2  - Leukemia Research
T1  - Prognostic significance of SOX2, SOX3, SOX11, SOX14 and SOX18 gene expression in adult de novo acute myeloid leukemia
EP  - 38
SP  - 32
VL  - 67
DO  - 10.1016/j.leukres.2018.02.001
ER  - 

@article{
author = "Tošić, Nataša and Petrović, Isidora and Kovačević Grujičić, Nataša and Davidović, Slobodan and Virijević, Marijana and Suvajdžić-Vuković, Nada and Pavlović, Sonja and Stevanović, Milena",
year = "2018",
abstract = "Aberrant expression of different SOX (SRY-related high mobility group (HMG) box) genes has been observed in number of tumors but, little is known about their expression patterns in hematological malignancies, especially in acute myeloid leukemia (AML). In this study we investigated SOX2, SOX3, SOX11, SOX14 and SOX18 gene expression in 50 de novo adult AML patients and correlated our findings with known clinical and molecular prognostic markers of the disease. We have found that these genes are overexpressed in 10-22% of patients and preliminary findings suggest that high expression level of these genes may have prognostic significance in AML patients. This is the first study focused on examining the expression level of SOX2, SOX3, SOX11, SOX14 and SOX18 genes in AML patients. Although this is a relatively limited study, initial findings indicate the need for further investigation of these genes, their potential roles in leukemia pathogenesis as well as prognosis in AML patients.",
publisher = "Pergamon-Elsevier Science Ltd, Oxford",
journal = "Leukemia Research",
title = "Prognostic significance of SOX2, SOX3, SOX11, SOX14 and SOX18 gene expression in adult de novo acute myeloid leukemia",
pages = "38-32",
volume = "67",
doi = "10.1016/j.leukres.2018.02.001"
}

Tošić, N., Petrović, I., Kovačević Grujičić, N., Davidović, S., Virijević, M., Suvajdžić-Vuković, N., Pavlović, S.,& Stevanović, M.. (2018). Prognostic significance of SOX2, SOX3, SOX11, SOX14 and SOX18 gene expression in adult de novo acute myeloid leukemia. in Leukemia Research
Pergamon-Elsevier Science Ltd, Oxford., 67, 32-38.
https://doi.org/10.1016/j.leukres.2018.02.001

Tošić N, Petrović I, Kovačević Grujičić N, Davidović S, Virijević M, Suvajdžić-Vuković N, Pavlović S, Stevanović M. Prognostic significance of SOX2, SOX3, SOX11, SOX14 and SOX18 gene expression in adult de novo acute myeloid leukemia. in Leukemia Research. 2018;67:32-38.
doi:10.1016/j.leukres.2018.02.001 .

Tošić, Nataša, Petrović, Isidora, Kovačević Grujičić, Nataša, Davidović, Slobodan, Virijević, Marijana, Suvajdžić-Vuković, Nada, Pavlović, Sonja, Stevanović, Milena, "Prognostic significance of SOX2, SOX3, SOX11, SOX14 and SOX18 gene expression in adult de novo acute myeloid leukemia" in Leukemia Research, 67 (2018):32-38,
https://doi.org/10.1016/j.leukres.2018.02.001 . .

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  - 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 . .