Objective. to determine the association between the expression of lipoprotein lipase (LPL) and c-MYC genes in peripheral blood cells of chronic lymphocytic leukemia (CLL) patients affected by the Chornobyl catastrophe depending on the mutational status of IGHV genes. Methods. Analysis was performed in the group of 69 CLL patients irradiated due to the Chornobyl NPP accident (58 clean-up workers of 1986 year, 6 inhabitants of radionuclide contaminated areas, and 5 evacuees). The IGHV gene mutational status was studied by polymerase chain reaction (PCR) followed by direct sequencing. LPL and c-MYC expression was evaluated by Quantitative Real-time PCR. Data were analyzed with the SPSS software package, version 20.0. Results. Relative LPL expression levels in CLL samples ranged from 0 to 1663.5 (mean 138.47 ± 30.69, median 26.1). A strong correlation between individual LPL expression levels and IGHV mutational status was found (r = 0.684; p < 0.0001). The average relative c-MYC expression level was 5.7 ± 0.87 (median 2.86; range 0–48.5). No association between c-MYC expression and IGHV mutational status was found. Among unmutated IGHV cases, a correlation between LPL and c-MYC gene expression levels was identified: r = 0.351; p = 0.013. Conclusions. Our data confirm the dominant concept that unmutated IGHV CLL cases are more sensitive to the action of proliferative stimuli compared to mutated IGHV CLL cases. This is manifested by an increase in the expression of a functionally significant LPL gene, is one for the strongest negative prognostic markers in CLL. Key words: lymphocytic leukemia, LPL, c-MYC, IGHV genes, Chornobyl NPP accident.
Objective: to study clinical-hematological data and expression of the main and alternative transcripts of SORL1 gene in chronic lymphocytic leukemia (CLL) patients affected by the Chornobyl catastrophe. Methods. Analysis was performed in the main group of 34 CLL patients irradiated due to the Chornobyl NPP accident (30 clean-up workers, and 4 evacuees) and in the control group of 27 non-irradiated CLL patients. Groups of patients were comparable by age, sex, stage of disease, mutational status of IGHV genes. Expression of the main and alternative transcripts of SORL1 gene was evaluated by Quantitative Real-time polymerase chain reaction (PCR). The IGHV gene mutational status, TP53 and SF3B1 mutations were studied by PCR followed by direct sequencing. Data were analyzed with the SPSS software package, version 20.0. Results. Relative expression level of the main transcript of SORL1 gene was low (mean 1.71 ± 0.55, median 0.57), did not correlate with the IGHV gene mutational status, TP53 and SF3B1 mutations, stage of disease. The expression of B transcript was not detected, F transcript was expressed at a very low level in 9 patients. The average relative expression level of SORL1-Δ2 transcript was 14.1 ± 6.04 (median 3.48; range 0.01–90.51). The expression of SORL1-Δ2 transcript above the median was more frequent among patients on C stage (p = 0.001), and in patients with unmutated IGHV genes was associated with an extremely negative course of CLL (median of overall survival 9 months vs 61 months at low expression). Relative expression levels of the main and alternative transcripts of SORL1 gene in patients of the main and the control groups did not differ. Conclusions. Our preliminary data suggest that increased expression of SORL1-Δ2 transcript in CLL patients with unmutated IGHV genes can be considered as a negative prognostic marker. Key words: chronic lymphocytic leukemia, SORL1, SORL1-Δ2, Chornobyl NPP accident.
Summary. Aim: To assess the expression of Ki-67 protein and CD34 antigen on peripheral blood (PB) and bone marrow (BM) cells in chronic myelogenous leukemia (CML) patients with different response to tyrosine kinase inhibitors (TKI) imatinib (IM) and nilotinib (NI) therapy. Patients and Methods: BM aspirate and PB samples from 41 CML patients treated with IM and NI were studied by cytogenetic, molecular genetic, and flow cytometry methods. According to the response to TKIs, the patients were distributed into the optimal response, warning, and treatment failure groups. Results: The patients with optimal response to TKI therapy showed the lowest levels of Ki-67 expression in PB and BM compared with the patients from warning and falure treatment groups, however, Ki-67 expression was close to the reference values in PB (0.7 ± 0.3)%, only in NI-treated patients, The highest expression of Ki-67 in PB was observed in patients from treatment failure groups. In PB of patients who received NI and did not achieve optimal response, CD34+ cell count increased by almost 4 times compared with that in the optimal response group. The results indicated that CD34+ cell pool expanded in patients with poor response to both IM and NI. In patients with optimal response to NI therapy, CD34+ cell counts in PB were within the reference range and did not exceed 0.5%. Similar results were observed for Ki-67 and CD34+ in BM hematopoietic cells. Conclusions: Ki-67 expression and CD34+ cell count in PB and BM of CML patients increased with the acquisition of clonal resistance to IM and NI. NI provides a deeper molecular response compared with IM.
Описано клінічний випадок застосування ритуксимабу для лікування постраждалого внаслідок аварії на Чорно бильській АЕС зі злоякісною резистентною формою міастенії у поєднанні з хронічною мікст інфекцією токсоп лазмами, вірусами Епштейна Барр, цитомегалії і простого герпесу. У динаміці дворічного спостереження пока зана клінічна ефективність моноклональних антитіл у вигляді стабілізації основних симптомів і зниження доз антихолінестеразної і глюкортикоїдної терапії. Позитивний ефект відмічався в найближчий і віддалений періоди. Враховуючи ефективність, безпечність і добру переносимість ритуксимабу, його доцільно рекоменду вати для лікування осіб, які зазнали впливу іонізуючої радіації і захворіли на міастенію, асоційовану з хронічною мікст інфекцією токсоплазмами, вірусами Епштейна Барр, цитомегалії і простого герпесу.
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