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Information × Registration Number 0214U002305, 0113U002315 , R & D reports Title Study of the molecular-genetic mechanisms of resistance to the tyrosine kinase inhibitor therapy in patients with chronic myeloid leukemia and reasoning of resistance overcoming ways popup.stage_title Head Dyagil I.S., Minchenko J.M., Registration Date 28-01-2014 Organization State institution "National research centеr for radiation medicine of the National academy of medical sciences of Ukraine " popup.description2 The object of study is patients with chronic myeloid leukemia who are initially resistant to tyrosine kinase inhibitor therapy. The aim - to determine the clinical course of the disease and cytogenetic , molecular genetic, morphological , immunogenetic characteristics of the tumor clone in patients with chronic myeloid leukemia with primary resistance to tyrosine kinase inhibitor treatment . Methods: hematologic, cytogenetic , molecular genetic, immunogenetic , cultural and statistics . The study involved 56 patients with CML initially resistant to imatinib therapy. Among the examined patients with CML 3 people were affected by the Chernobyl accident . In the study group of patients with CML initially resistant to imatinib therapy , most patients at the 6th month of therapy has been achieved complete hematology response, but the level of cells with translocation t (9;22) was maintained between 95 and 100%. It was determined that in 10% of patients studied in this group additional clonal chromosome aberrations (except for the specific translocation t( 9;22)) were found. In 7 % of patients additional Ph- chromosome was revealed. It was shown, that in patients with CML initially resistant to imatinib therapy, mutations that cause this resistance dominated. These cases require to switch on the II generation TKI or use allo-HSCT. The necessity of histotyping after 6 months of TKI therapy was proved in patients with high risk of primary resistance for using allol-HSCT as a treatment option. It was shown that imatinib as a target therapy of chronic phase CML leads to a gradual normalization of secretion of proinflammatory cytokines (IL -1?, IL-6 , IL -8) and anti-inflammatory cytokines ( IL -4 , IL-10). The high colony-formation efficiency of progenitor cells and fibroblasts colony forming, indicated only partial inhibition of specific proliferation of bone marrow cells in patients with CML initially resistant to imatinib therapy. Complex of unfavorable CML flow features , indicating the formation of primary resistance to TKI was composed. It included intermediate and high Sokal prognostic index , the presence of additional clonal rearrangements of karyotype , the appearance of mutations , imbalance of pro-inflammatory and anti-inflammatory cytokines, maintaining high proliferative activity of hematopoietic cells. Product Description popup.authors Балан Валентина Володимирівна Дмитренко Ірина Віталіївна Дмитренко Олена Олександрівна Любарець Тетяна Федорівна Малінкіна Тетяна Володимирівна Федоренко Віра Григорівна Шляхтиченко Тетяна Юрівна Шолойко Валентина Василівна popup.nrat_date 2020-04-02 Close