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.

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This work was supported by the Russian Science Foundation (project no. 18-15-00398).

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Correspondence to T. V. Nasedkina.

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Conflict of interest. The authors declare no conflict of interest.

Statement of compliance with standards of research involving humans as subjects. All procedures performed in this work comply with the ethical standards of the institutional committee for research ethics and the Helsinki Declaration of 1964 and its subsequent changes or comparable ethical standards. Written voluntary informed consent was obtained from the parents of patients to use the results of the study anonymously for scientific purposes.

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Translated by I. Shipounova

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Ghukasyan, L.G., Krasnov, G.S., Muravenko, O.V. et al. Driver Mutations in Acute Myeloid Leukemia with Inversion of Chromosome 16. Mol Biol 54, 341–348 (2020).

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  • massive parallel sequencing
  • acute myeloid leukemia
  • somatic mutations
  • inversion 16