[Driver Mutations in Acute Myeloid Leukemia with Inversion of Chromosome 16].

Certain subtypes of acute myeloid leukemia occur as a result of the cooperation of several events these are, 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 associated with different chromosomal disorders. However, the role of mutation events in malignant cell transformation processes remains obscure. We searched for driver mutation events in leukemic cells containing the chimeric CBFB-MYH11 gene, which results from inversion of chromosome 16. Using target enrichment, the coding regions of 84 genes in genomes of 12 children with acute myeloid leukemia with inv(16) were investigated. Somatic mutations have been found in the genes of the proteins of intracellular signaling cascades mediated by receptor tyrosine kinases, such as KIT (41%), NRAS (25%), KRAS (17%), and 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 undescribed mutations in the KDM6A, NOTCH1, and IDH1 genes, which may be involved in leukemogenesis processes have been identified.

[Mutational Profiling of Pediatric Myeloid Leukemia Subtypes without Clinically Significant Chromosomal Aberrations].

The discovery of novel significant molecular and genetic markers is important for the diagnostics, prognosis, and therapy selection in hematological malignancies. Distinct cytogenetic aberrations leading to the formation of fusion genes are found in more than 40% of pediactric cases of acute myeloid leukemia (AML); however, the tumor cells in approximately 20% of these patients display cytogenetically normal karyotype (NK-AML). Here we present the analysis of the mutational profiles of leukemic cells collected from pediatric AML cases without known clinically significant chromosomal aberrations aimed at identifying AML specific markers. In 34 pediatric cases of different AML types, the coding regions of 26 genes involved in the AML pathogenesis were analyzed by massive parallel sequencing. Sequencing revealed the somatic mutations in genes that are involved in various intracellular signaling pathways, including the CEBPA, ETV, IDH1, JAK2, and NRAS genes. In addition, rare genetic variants were found in CUX1, FLT3, TET2, PTPN11, and NUP98 genes. This data may contribute to the understanding of the mechanisms of malignant cell transformation in the case of leukemogenesis.