Browsing by Author "Palibrk, Vuk (57193509237)"

Dysregulation of apoptosis is a distinctive feature of chronic lymphocytic leukemia (CLL), although a unique mechanism underlying apoptosis resistance of CLL B lymphocytes has not been identified yet. Aberrant expression as well as genetic and epigenetic alterations of numerous genes involved in different pathways of apoptosis regulation has been described in CLL. Here, we report the expression analysis of Bcl2L12 (Bcl2-like 12), a novel apoptotic gene belonging to Bcl2 family, in 58 Serbian CLL patients. Quantitative reverse-transcriptase polymerase chain reaction (qRT-PCR) analysis revealed a significant overexpression of Bcl2L12 mRNA in CLL samples compared to non-leukemic samples, implying its role in the pathogenesis of the disease. Receiver operating characteristic (ROC) analysis showed that Bcl2L12 expression efficiently discriminates CLL cases from healthy controls. However, relatively homogenous Bcl2L12 mRNA expression among patients did not reflect their clinical characteristics (with the exception of lactate dehydrogenase status and time from diagnosis to treatment) and failed to show association with the most informative prognostic markers, namely the mutational status of rearranged immunoglobulin heavy chain variable region genes, CD38 and lipoprotein lipase gene (LPL) expression. © 2013 Springer Science+Business Media New York.

Dysregulation of apoptosis is a distinctive feature of chronic lymphocytic leukemia (CLL), although a unique mechanism underlying apoptosis resistance of CLL B lymphocytes has not been identified yet. Aberrant expression as well as genetic and epigenetic alterations of numerous genes involved in different pathways of apoptosis regulation has been described in CLL. Here, we report the expression analysis of Bcl2L12 (Bcl2-like 12), a novel apoptotic gene belonging to Bcl2 family, in 58 Serbian CLL patients. Quantitative reverse-transcriptase polymerase chain reaction (qRT-PCR) analysis revealed a significant overexpression of Bcl2L12 mRNA in CLL samples compared to non-leukemic samples, implying its role in the pathogenesis of the disease. Receiver operating characteristic (ROC) analysis showed that Bcl2L12 expression efficiently discriminates CLL cases from healthy controls. However, relatively homogenous Bcl2L12 mRNA expression among patients did not reflect their clinical characteristics (with the exception of lactate dehydrogenase status and time from diagnosis to treatment) and failed to show association with the most informative prognostic markers, namely the mutational status of rearranged immunoglobulin heavy chain variable region genes, CD38 and lipoprotein lipase gene (LPL) expression. © 2013 Springer Science+Business Media New York.

Background: Chronic lymphocytic leukemia (CLL) results from the clonal expansion of mature B lymphocytes and is characterized by extreme clinical heterogeneity. One of the most reliable prognostic markers in chronic lymphocytic leukemia (CLL) is the mutational status of immunoglobulin heavy variable (IGHV) genes, which defines 2 subsets, mutated CLL (M-CLL) and unmutated CLL (U-CLL), with different clinical courses. Biased IGHV gene use between M-CLL and U-CLL clones, as well as population differences in the IGHV gene repertoire have been reported. Patients and Methods: In this study, mutational status and configuration of IGHV-IGHD-IGHJ rearrangements in 85 Serbian patients were analyzed using reverse transcriptase-polymerase chain reaction (RT-PCR) and sequencing methodology. Results: We found that 55.3% of cases belonged to M-CLL and 44.7% belonged to U-CLL, with progressive disease predominating in the unmutated subset. Most frequently expressed was the IGHV3 subgroup (55.7%), followed by IGHV1 (27.3%), IGHV4 (12.5%), IGHV5 (2.3%), IGHV2 (1.1%), and IGHV6 (1.1%). The distribution of IGHD subgroups was as follows: IGHD3, 39.1%; IGHD2, 21.8%; IGHD6, 12.6%; IGHD1, 10.3%; IGHD4, 8%; IGHD5, 6.9%; and IGHD7, 1.1%. The most frequent IGHJ gene was IGHJ4 (48.9%), followed by IGHJ6 (28.4%), IGHJ3 (11.4%), and IGHJ5 (11.4%). In 15.3% of cases, heavy complementarity-determining region 3 (VH CDR3) amino acid sequences could be assigned to previously defined stereotyped clusters. Conclusions: Our study showed a strong correlation between IGHV gene mutational status and clinical course of CLL. IGHV gene use was comparable to that obtained for Mediterranean countries, with the exception of the IGHV4 subgroup, which was underrepresented in our cohort. © 2012 Elsevier Inc. All rights reserved.

Background: Chronic lymphocytic leukemia (CLL) results from the clonal expansion of mature B lymphocytes and is characterized by extreme clinical heterogeneity. One of the most reliable prognostic markers in chronic lymphocytic leukemia (CLL) is the mutational status of immunoglobulin heavy variable (IGHV) genes, which defines 2 subsets, mutated CLL (M-CLL) and unmutated CLL (U-CLL), with different clinical courses. Biased IGHV gene use between M-CLL and U-CLL clones, as well as population differences in the IGHV gene repertoire have been reported. Patients and Methods: In this study, mutational status and configuration of IGHV-IGHD-IGHJ rearrangements in 85 Serbian patients were analyzed using reverse transcriptase-polymerase chain reaction (RT-PCR) and sequencing methodology. Results: We found that 55.3% of cases belonged to M-CLL and 44.7% belonged to U-CLL, with progressive disease predominating in the unmutated subset. Most frequently expressed was the IGHV3 subgroup (55.7%), followed by IGHV1 (27.3%), IGHV4 (12.5%), IGHV5 (2.3%), IGHV2 (1.1%), and IGHV6 (1.1%). The distribution of IGHD subgroups was as follows: IGHD3, 39.1%; IGHD2, 21.8%; IGHD6, 12.6%; IGHD1, 10.3%; IGHD4, 8%; IGHD5, 6.9%; and IGHD7, 1.1%. The most frequent IGHJ gene was IGHJ4 (48.9%), followed by IGHJ6 (28.4%), IGHJ3 (11.4%), and IGHJ5 (11.4%). In 15.3% of cases, heavy complementarity-determining region 3 (VH CDR3) amino acid sequences could be assigned to previously defined stereotyped clusters. Conclusions: Our study showed a strong correlation between IGHV gene mutational status and clinical course of CLL. IGHV gene use was comparable to that obtained for Mediterranean countries, with the exception of the IGHV4 subgroup, which was underrepresented in our cohort. © 2012 Elsevier Inc. All rights reserved.

Introduction Sjógren's syndrome is a chronic autoimmune disorder carrying the risk of the development of non-Hodgkin's lymphoma, most frequently marginal zone lymphoma. Case Outline A 66-year-old male patient with Sjógren's syndrome, after a year of the disease, developed a nodal marginal zone lymphoma with lymphoma cells in peripheral blood which had the following immunophenotype: CD19, CD20, CD22, CD19/kappa, CD79b+. After six cycles of chemotherapy according to CHOP protocol (cyclophosphamide, doxorubicin, vincristine and prednisone) disease remission was achieved lasting four months, followed by enlargement of lymph nodes in all areas (generalized lymphadenopathy), splenomegaly and enlargement of the right parotid gland. Bone marrow biopsy and histology confirmed lymphoma of the same morphologic and immunohistochemic profile. Biopsy of a very enlarged hard right parotid gland, by using histology and immunohistochemistry, showed lymphoid tumour tissue with blast appearance and a number of nucleoli corresponding to centroblasts and less to immunoblasts. Immunophenotypes of these cells were as follows: CD79alfa+, CD20+, CD3-, bcl-2-; proliferative activity measured with KI-67 was high rating 60%. Histology and immunohistochemistry showed the co-existence of a diffuse large B cell lymphoma with marginal zone lymphoma. In spite of aggressive chemotherapy treatment according to protocol ESHAP (Vepesid 200 mg i.v. on 1st and 2nd day and 100 mg on 3rd, 4th and 5th day; Cisplatin 20-20-10 mg on 1st to 4th day) the disease showed a progressive course. Conclusion In patients with Sjógren's syndrome, the possibility of lymphoma should be kept in mind and in suspected cases timely diagnostic and therapeutic measures should be undertaken.