Browsing by Author "Suvajdzic Vukovic, Nada (7003417452)"

The objective of the study was to investigate factors related to the occurrence of myelodysplatic syndromes (MDS) in the population of Belgrade (Serbia Montenegro). The case-control study was conducted during the period 2000-2003. The study group consisted of 80 newly diagnosed MDS patients and 160 sex- and age-matched hospital controls with nonmalignant and noninfectious diseases. The disease categories in the control group were circulatory (51 patients, 32%), gastrointestinal (53 patients, 33%), and ophthalmological (56 patients, 35%) disorders. Conditional univariate and multivariate logistic regression analyses were applied. Multivariate analysis showed the following factors to be significantly related to MDS: exposure to chemicals (OR=10.8, 95%CI 3.2-36.2, p=0.0001), viral upper respiratory tract infections (twice a year or more, OR=5.8, 95%CI 2.5-13.6, p=0.0001), exposure to insecticides, pesticides and herbicides (OR=5.2, 95%CI 1.8-15.1, p=0.003), coffee (OR=5.1, 95%CI 1.9-13.7, p=0.001), and alcohol consumption (OR=2.2, 95%CI 1.1-4.6, p=0.033). The findings support the hypotheses that exposure to chemical agents, pesticides, insecticides, and herbicides, certain lifestyle factors (alcohol and coffee consumption), and frequent viral infections may be involved in the etiology of MDS, but these results should be confirmed by further investigations. © Springer-Verlag 2006.

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). 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. 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. 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. © 2019 Dragana Janic, Jelena Peric, Teodora Karan-Djurasevic, Tatjana Kostic, Irena Marjanovic, Bojana Stanic, Nadja Pejanovic, Lidija Dokmanovic, Jelena Lazic, Nada Krstovski, Marijana Virijevic, Dragica Tomin, Ana Vidovic, Nada Suvajdzic Vukovic, Sonja Pavlovic, Natasa Tosic, published by Sciendo.

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). 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. 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. 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. © 2019 Dragana Janic, Jelena Peric, Teodora Karan-Djurasevic, Tatjana Kostic, Irena Marjanovic, Bojana Stanic, Nadja Pejanovic, Lidija Dokmanovic, Jelena Lazic, Nada Krstovski, Marijana Virijevic, Dragica Tomin, Ana Vidovic, Nada Suvajdzic Vukovic, Sonja Pavlovic, Natasa Tosic, published by Sciendo.

Introduction: We evaluated a novel approach for investigation of lymphocyte dysregulation in Gaucher patients by including determination of IgH and TCR gene rearrangements together with levels of immunoglobulins, natural autoantibodies as well as presence of monoclonal protein. Materials and methods: Measurement of serum immunoglobulins, monoclonal immunoglobulins, selected autoantibodies, as well as analysis of immunoglobulin heavy chain and T cell receptor gene rearrangements. Results: Immunoglobulin disorder was detected in 29.6% patients, 40.7% demonstrated presence of B cell clonality and 44.4% demonstrated presence of autoantibodies. In five patients in our series, the presence of IgH gene rearrangement was the only detectable indicator of B cell dysfunction. TCR gene rearrangements were not found in any of the patients. Conclusion: Based on our results, we propose IgH gene rearrangements as a new biomarker for investigation of B cell dysfunction occurring as a complication of Gaucher disease. © 2012 Elsevier Inc.

Introduction: We evaluated a novel approach for investigation of lymphocyte dysregulation in Gaucher patients by including determination of IgH and TCR gene rearrangements together with levels of immunoglobulins, natural autoantibodies as well as presence of monoclonal protein. Materials and methods: Measurement of serum immunoglobulins, monoclonal immunoglobulins, selected autoantibodies, as well as analysis of immunoglobulin heavy chain and T cell receptor gene rearrangements. Results: Immunoglobulin disorder was detected in 29.6% patients, 40.7% demonstrated presence of B cell clonality and 44.4% demonstrated presence of autoantibodies. In five patients in our series, the presence of IgH gene rearrangement was the only detectable indicator of B cell dysfunction. TCR gene rearrangements were not found in any of the patients. Conclusion: Based on our results, we propose IgH gene rearrangements as a new biomarker for investigation of B cell dysfunction occurring as a complication of Gaucher disease. © 2012 Elsevier Inc.

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 (WT1high status), present in 25.5% of patients, was an independent unfavorable factor for achieving complete remission. WT1high 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 < 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 WT1high 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. © 2017 Elsevier Inc.

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 (WT1high status), present in 25.5% of patients, was an independent unfavorable factor for achieving complete remission. WT1high 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 < 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 WT1high 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. © 2017 Elsevier Inc.