Browsing by Author "Kraguljac-Kurtović, Nada (37037758700)"

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 62-year-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. © 2020 Inst. Sci. inf., Univ. Defence in Belgrade. All rights reserved.

Introduction B-cell chronic lymphocytic leukemia (CLL) can be easily overlooked in pregnancy, particu-larly in cases with inadequate antenatal care. We report a case of pregnant woman diagnosed with CLL and evaluate this patient with cases in literature. Case report An asymptomatic 35-year-old woman presented with slightly elevated absolute lympho-cyte count at antenatal monitoring in her second pregnancy. Further hematological investigations dis-closed CLL with monoallelic deletion of chromosome 13q14. She was monitored during throughout the pregnancy, being asymptomatic and without treatment, and delivered a healthy child at term with no complications. After almost four years of follow up patient is without any signs of disease progression and her absolute lymphocyte counts remained on predelivery levels. This is the first published case of CLL diagnosed during pregnancy in Serbia. Rare similar cases published so far have been discussed, especially in terms of disease course, long-term prognosis and available therapeutic modalities. Conclusion Due to the fact that nowadays many women are delaying childbearing in middle age it can be expected that cancer diagnose could be more often found in pregnant women in the future. In a view of the complex nature of such condition, a multidisciplinary approach for diagnosing and treating of pregnant women is highly recommended. © 2022, Serbia Medical Society. All rights reserved.

Introduction: The impact of activated blood and endothelial cells on the thrombosis in myeloproliferative neoplasms (MPN) has not yet been clarified. We prospectively analyzed correlation between circulating leukocyte-platelet aggregates and soluble selectins to thrombosis occurrence in MPN, in the context of standard and cardiovascular risk factors, and different clinical and biological characteristics. Methods: Flow cytometric analysis of neutrophil-platelet (Neu-Plt) and monocyte-platelet (Mo-Plt) aggregates in peripheral blood, as well as quantification of soluble E-/L-/P-selectins by enzyme immunoassay, was performed on 95 newly diagnosed MPN patients. Results: During the follow-up, thrombosis occurred in 12.6% MPN patients (arterial 9.4%, venous 3.2%), with a mean time of 39 months. The overall incidence rate of main thrombotic events was 4.36 per 100 patient-years. The incidence of arterial hypertension (HTA) was significantly higher in patients with thrombosis, compared to those without thrombosis (P <.05). The level of soluble P-selectin was significantly higher in patients with thrombosis compared to those without thrombosis (346.89 ng/mL vs 286.39 ng/mL, P =.034). The mean level of Neu-Plt (26.7% vs 22.4%) and Mo-Plt (17.8% vs 12.3%) aggregates did not differ significantly between the groups with and without thrombosis. A multivariate COX proportional hazard regression model confirmed an independent predictive significance of Mo-Plt aggregates (HR = 1.561, 95% CI: 1.007-2.420, P =.046), as well as the cumulative effect of Mo-Plt aggregates and HTA (HR = 1.975, 95%CI: 1.215-3.212, P =.006) for thrombosis occurrence. Conclusion: Monocyte-platelet aggregates represent an independent risk factor for thrombosis occurrence, further on supported by HTA. © 2021 John Wiley & Sons Ltd

Introduction: The impact of activated blood and endothelial cells on the thrombosis in myeloproliferative neoplasms (MPN) has not yet been clarified. We prospectively analyzed correlation between circulating leukocyte-platelet aggregates and soluble selectins to thrombosis occurrence in MPN, in the context of standard and cardiovascular risk factors, and different clinical and biological characteristics. Methods: Flow cytometric analysis of neutrophil-platelet (Neu-Plt) and monocyte-platelet (Mo-Plt) aggregates in peripheral blood, as well as quantification of soluble E-/L-/P-selectins by enzyme immunoassay, was performed on 95 newly diagnosed MPN patients. Results: During the follow-up, thrombosis occurred in 12.6% MPN patients (arterial 9.4%, venous 3.2%), with a mean time of 39 months. The overall incidence rate of main thrombotic events was 4.36 per 100 patient-years. The incidence of arterial hypertension (HTA) was significantly higher in patients with thrombosis, compared to those without thrombosis (P <.05). The level of soluble P-selectin was significantly higher in patients with thrombosis compared to those without thrombosis (346.89 ng/mL vs 286.39 ng/mL, P =.034). The mean level of Neu-Plt (26.7% vs 22.4%) and Mo-Plt (17.8% vs 12.3%) aggregates did not differ significantly between the groups with and without thrombosis. A multivariate COX proportional hazard regression model confirmed an independent predictive significance of Mo-Plt aggregates (HR = 1.561, 95% CI: 1.007-2.420, P =.046), as well as the cumulative effect of Mo-Plt aggregates and HTA (HR = 1.975, 95%CI: 1.215-3.212, P =.006) for thrombosis occurrence. Conclusion: Monocyte-platelet aggregates represent an independent risk factor for thrombosis occurrence, further on supported by HTA. © 2021 John Wiley & Sons Ltd

Purpose: We compared the gene expression profile of peripheral blood CD34+ cells and granulocytes in subjects with chronic myeloid leukemia (CML), with the accent on signaling pathways affected by BCR-ABL oncogene. Methods: The microarray analyses have been performed in circulating CD34+ cells and granulocytes from peripheral blood of 7 subjects with CML and 7 healthy donors. All studied BCR-ABL positive CML patients were in chronic phase, with a mean value of 2012±SD of CD34+cells/μl in peripheral blood. Results: The gene expression profile was more prominent in CML CD34+ cells (3553 genes) compared to granulocytes (2701 genes). The 41 and 39 genes were significantly upregulated in CML CD34+ cells (HINT1, TXN, SERBP1) and granulocytes, respectively. BCR-ABL oncogene activated PI3K/AKT and MAPK signaling through significant upregulation of PTPN11, CDK4/6, and MYC and reduction of E2F1, KRAS, and NFKBIA gene expression in CD34+ cells. Among genes linked to the inhibition of cellular proliferation by BCR-ABL inhibitor Imatinib, the FOS and STAT1 demonstrated significantly decreased expression in CML. Conclusion: The presence of BCR-ABL fusion gene doubled the expression quantity of genes involved in the regulation of cell cycle, proliferation and apoptosis of CD34+ cells. These results determined the modified genes in PI3K/AKT and MAPK signaling of CML subjects. © 2015 Elsevier Inc.

Purpose: We compared the gene expression profile of peripheral blood CD34+ cells and granulocytes in subjects with chronic myeloid leukemia (CML), with the accent on signaling pathways affected by BCR-ABL oncogene. Methods: The microarray analyses have been performed in circulating CD34+ cells and granulocytes from peripheral blood of 7 subjects with CML and 7 healthy donors. All studied BCR-ABL positive CML patients were in chronic phase, with a mean value of 2012±SD of CD34+cells/μl in peripheral blood. Results: The gene expression profile was more prominent in CML CD34+ cells (3553 genes) compared to granulocytes (2701 genes). The 41 and 39 genes were significantly upregulated in CML CD34+ cells (HINT1, TXN, SERBP1) and granulocytes, respectively. BCR-ABL oncogene activated PI3K/AKT and MAPK signaling through significant upregulation of PTPN11, CDK4/6, and MYC and reduction of E2F1, KRAS, and NFKBIA gene expression in CD34+ cells. Among genes linked to the inhibition of cellular proliferation by BCR-ABL inhibitor Imatinib, the FOS and STAT1 demonstrated significantly decreased expression in CML. Conclusion: The presence of BCR-ABL fusion gene doubled the expression quantity of genes involved in the regulation of cell cycle, proliferation and apoptosis of CD34+ cells. These results determined the modified genes in PI3K/AKT and MAPK signaling of CML subjects. © 2015 Elsevier Inc.

Introduction. The emergence of multiple myeloma as a second malignancy in patients with essential thrombocythemia is extremely rare. Several cases have been published so far, pointing out the impact of a cytotoxic effect during treatment of essential thrombocythemia on the development of multiple myeloma. Case presentation. We report the case of a 52-year-old Caucasian man who presented to our hospital because of leukocytosis, a slightly decreased hemoglobin level and thrombocytosis. After a complete hematological work-up, essential thrombocythemia was diagnosed. The patient was included in a multicenter clinical study, treated with anagrelide and his platelet counts were maintained in the normal range for more than 3 years. A sudden drop in his hemoglobin level with normal leukocyte and platelet count occurred at the same time as a back pain. Magnetic resonance imaging of his spine revealed the existence of a pathological fracture of Th4, the collapse of the upper edge of Th7 and osteolytic lesions of multiple thoracic vertebrae. Repeated hematological examinations, including bone biopsy with immunohistochemistry, disclosed diagnosis of multiple myeloma of the non-secretory type. Conclusions: To the best of our knowledge this is the first published case in which multiple myeloma developed during the treatment of essential thrombocythemia with the non-cytotoxic drug anagrelide. Our attempts to find a common origin for the coexistence of multiple myeloma and essential thrombocythemia have not confirmed the genetic basis of their appearance. Further studies are needed to determine the biological impact of this coexistence. © 2013Leković et al.; licensee BioMed Central Ltd.