Search academic texts

Information × Registration Number 0218U001411, 0116U003574 , R & D reports Title The role of BCR/ABL gene mutations, chromosome, molecular genetic abnormalities and immunogenetic parameters in formation of approaches to optimization of target therapy in patients with chronic myeloid leukemia in the remote period after the Chornobyl power plant accident. popup.stage_title Head Dyagil I.S., Minchenko J.M., Registration Date 08-02-2018 Organization State institution "National research centеr for radiation medicine of the National academy of medical sciences of Ukraine " popup.description2 The object of the study - patients with chronic myeloid leukemia with failure of tyrosine kinase inhibitors therapy (TKI). The aim of the work is to determine the effect of BCR/ABL gene mutations, as well as chromosomal, molecular genetic abnormalities and immunogenicity parameters on the resistance to TKI therapy in patients with chronic myeloid leukemia. Research methods - hematological, cytogenetic, molecular genetic, immunogenetic, cultural and statistical. Research results. We examined 62 CML patients with resistance to TKI from the general population and 29 patients who were exposed in results of Chernobyl power plant accident. A statistically significant decrease in the overall 5-year survival (p = 0.020), event-free survival (p = 0.015) and progression-free survival was found in patients with additional chromosomal aberrations in Ph-positive cells (p = 0.039). In a group of irradiated patients (29 patients), the mutation rate is 71%. The presence of mutations in the BCR/ABL gene significantly reduces the likelihood of achieving a complete cytogenetic response (20% vs. 97%), and virtually prevents the achievement of a major molecular response. BCR/ABL gene mutations are associated with decreasing the efficacy of TKI therapy, and a reduction of progression-free survival (p <0.001), a event-free (p <0.001) and overall survival (p <0.001). The lack of reduction of BCR/ABL1 gene expression below 10 % on the 3rd month of imatinib therapy is an early criterion for adverse prediction of a complete cytogenetic and major molecular response to TKI therapy and is associated with a high probability of therapy resistance development. A set of features of the clinical course of CML, chromosomal abnormalities and the spectrum of mutations in the kinase domain of the BCR/ABL gene, which determine the formation of resistance to tyrosine kinase inhibitors therapy in patients with chronic myeloid leukemia, is selected, namely: the intermediate and high Sokal index, the presence of additional clonal alterations in Ph -positive cells, the appearance of mutations in the kinase domain of the BCR/ABL gene, carrier of HLA-DRB1*11, high levels of IL-8 (more 41.3 ± 1.32) pg / ml and low level of IL-2 concentrations (less 4.3 ± 0.65) and IFN-gamma, expression level of the fusion BCR/ABL gene more than 10 % on the 3rd month of itamtinib treatment, maintaining high proliferative activity of hematopoietic cells. Product Description popup.authors Балан Валентина Володимирівна Дмитренко Ірина Віталіївна Дмитренко Олена Олександрівна Малінкіна Тетяна Володимирівна Мартіна Зоя Володимирівна Парамонов Віктор Володимирович Федоренко Віра Григорівна Шляхтиченко Тетяна Юрівна Шолойко Валентина Василівна popup.nrat_date 2020-04-02 Close