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Information × Registration Number 0222U000736, 0119U100872 , R & D reports Title The value of molecular genetic disturbances in predicting of the response to the second line therapy with tyrosine kinase inhibitors in patients with chronic myeloid leukemia, resistant to imatinib, exposed to ionizing radiation due to Chornobyl PPS accident popup.stage_title Head Diahil Iryna S., Minchenko Jeanne M., Доктор біологічних наук Registration Date 18-01-2022 Organization State Institution "National Research Centre For Radiation Medicine of National Academy of Medical Sciences of Ukraine" popup.description2 In order to determine a set of molecular genetic prognostic criteria for response to second-line therapy with tyrosine kinase inhibitors to justify the personification of targeted therapy in patients with chronic myeloid leukemia resistant to imatinib, 223 patients were examined. Among them 27 patients were exposed to ionizing radiation as a result of the accident at the Chernobyl nuclear power plant. Clinical and hematological features of CML, which are associated with a high risk of resistance to imatinib therapy, were determined: intermediate and high prognostic Sokal index in the onset of the disease, the level of BCR/ABL1 gene expression > 10% after 3 months of nilotinib therapy. The second line of nilotinib therapy allowed to overcome resistance and achieve a complete cytogenetic response after 12 months of therapy mainly in patients with wild-type BCR/ABL1 gene (35.9% vs. 14.3% of patients). Normalization of the interleukin-2 level and increase in the interferon-γ concentration in CML patients with chronic phase on the second line of TKI therapy indicated a gradual normalization of immune reactivity. Among irradiated CML patients a high incidence of primary and secondary resistance to imatinib, as well as an increase in the frequency of mutations in the genes GATA2, STAG2, ASXL1, KDM6A, BCOR, CUX1, GNAS, KMT2A, SMC3, TET2, PHF6, DNMT3A, BCORL1, JAK2, TP53, HRAS, IKZF1, CARL in addition to the fusion BCR/ABL1 gene. A set of prognostic molecular genetic criteria, which determined the expediency of choosing nilotinib as the second line therapy for patients with CML for whom imatinib therapy was uneffective, has been developed, namely: reduction of tumor clone to complete cytogenetic response, low rate of clone with additional chromosome aberrations, absence of BCR/ABL1 kinase domain mutations and BCR/ABL1-independent mutations of somatic origin at the beginning of the second line therapy.  Product Description popup.authors Balan Valentyna Volodimirivna Dmytrenko Iryna Vitaliivna Dyagil Iryna Sergiivna Minchenko Jeanne M. Martina Zoya V Selina Iryna O Stupakova Zinaida V. Fedorenko Vira G. Shlyakhtychenko Tetiana Yu. Sholoiko Valentyna V. popup.nrat_date 2022-03-09 Close