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Information × Registration Number 0221U100615, 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 07-01-2021 Organization State Institution "National Research Centre For Radiation Medicine of National Academy of Medical Sciences of Ukraine" popup.description2 Forty seven patients with chronic myeloid leukemia (CML) were examined to determine the features of the clinical course, the dynamics of BCR/ABL1 fusion gene expression, cytogenetic response, the spectrum of BCR/ABL1 kinase domain mutations and the cytokine system in CML patients with different degrees of tumor clone reduction on second-line tyrosine kinase inhibitors (TKI) therapy. Among them 12 patients were exposed to ionizing radiation as a result of the Chernobyl nuclear power plant accident (ChNPPA). It was found that an increase in the number of Ph + cells and the percentage of metaphases with additional chromosomal aberrations before the start of the second line of TKI therapy was associated with a decrease in the probability of achieving a complete cytogenetic and major molecular responses. In patients with ВCR/ABL1 > 10% after 3 months of nilotinib therapy the likelihood of the achieving the complete cytogenetic and major molecular response was lower. Patients with BCR/ABL1 ≤ 1% after 6 months of nilotinib therapy had better 4-year event-free survival, progression-free survival, and overall survival. The second line of TKI therapy allowed to overcome resistance and achieve a complete cytogenetic response after 12 months mainly in patients with wild-type BCR/ABL1 gene. Normalization of interleukin-2 and increase of the interferon-γ concentration in CML patients on the second line of TKI therapy indicated a gradual normalization of immune reactivity. It was shown that the effectiveness of changing the TKI in cases of resistance to imatinib in patients exposed to ionizing radiation was the same as in the group of non-irradiated CML patients. A spectrum of clinical-hematological, cytogenetic and molecular-genetic characteristics of the tumor clone in CML patients on the second line of TKI therapy was formed, namely: intermediate and high Sokal score in disease onset, the presence of additional chromosomal aberrations and BCR/ABL1 kinase domain mutations. Product Description popup.authors Balan Valentyna V Dmytrenko Iryna V Martina Zoya V. Petrusha Oleksandr O Selina Iryna O Stupakova Zinaida V. Fedorenko Vira G Shliakhtychenko Tetiana Yu Sholoiko Valentyna V popup.nrat_date 2021-03-17 Close