Work

The presented work is devoted to the study of the association of replicative stress (RS) in blast cells of patients with acute myeloid leukemia with the expression of the c-MYC oncogene and immunophenotypic features of leukemic stem cells. RS is today considered one of the main factors that leads to genome instability and the development of malignant neoplasms of different genesis, including acute myeloid leukemia. It is believed that RS in tumor cells can occur as a result of a number of reasons, among which one of the main ones is the activation of oncogenes. In addition, there is evidence that high levels of RS may be observed in cancer stem cells and accompany the development of resistance to chemotherapy. RS is accompanied by an increase in the level of double-strand DNA breaks and activation of the ATR pathway, in particular, such components as Chk1 and Claspin. During the project, the expression of the c-MYC oncogene, the level of double-stranded DNA breaks and the expression of the CHEK1 and Claspin genes that are involved in adaptation to RS will be determined in the blast cells of patients with acute myeloid leukemia. A comparative analysis of the expression of the c-MYC, CHEK1 and Claspin genes, as well as the level of double-stranded DNA breaks, taking into account the immunophenotypic characteristics of blast cells in patients with acute myeloid leukemia, will be carried out. Based on the data obtained, it will be concluded whether oncogene-induced RS mediated by c-MYC is associated with the characteristics and stem cells counts in acute myeloid leukemia. The results obtained will deepen the understanding of the role of RS in determining the biological characteristics of acute myeloid leukemia and may become a fundamental basis for the search for new approaches to therapy aimed at inhibiting ATR-mediated responses to RS and overcoming chemoresistance.