DRIVER MUTATIONS IN ACUTE MYELOID LEUKEMIAWITH INVERSION OF CHROMOSOME 16
The formation of certain subtypes of acute myeloid leukemia occurs as a result of the cooperation of several events: the formation of fusion genes as a result of chromosomal rearrangements, which leads to the disruption of cell differentiation, and the emergence of mutations that enhance cellular proliferation by activating intracellular signaling pathways. High-throughput sequencing methods reveal characteristic mutation spectra in leukemia with different chromosomal aberrations, however, the role of mutation events in malignant cell transformation processes remains open. The paper searched for driver mutation events in leukemic cells containing the chimeric CBFB-MYH11 gene, which results from the inversion on chromosome 16. Using target enrichment, the coding regions of 84 genes in 12 children in acute myeloid leukemia with inv(16) were investigated. Somatic mutations have been found in the genes of receptor tyrosine kinase-mediated intracellular signaling cascades such as KIT (41%), NRAS (25%), KRAS (17%), FLT3 (8.3%). Comparative analysis of samples at the time of diagnosis and during remission was used to assess the role of mutations in the pathogenesis of the disease. Previously not described mutations in KDM6A genes, NOTCH1, IDH1, which may be involved in leukemogenesis processes have been identified.