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 proliferat...

Full description

Saved in:
Bibliographic Details
Published in:Molecular biology (New York) 2020-05, Vol.54 (3), p.341-348
Main Authors: Ghukasyan, L. G., Krasnov, G. S., Muravenko, O. V., Ikonnikova, A. Y., Yurasov, R. A., Baidun, L. V., Ibragimova, S. Z., Nasedkina, T. V.
Format: Article
Language:English
Subjects:
Acute myeloid leukemia
Biochemistry
Biomedical and Life Sciences
Cell differentiation
Chromosome 16
Chromosome rearrangements
Comparative analysis
Genomes
Genomics. Transcriptomics
Human Genetics
Intracellular
Intracellular signalling
Inversion
Leukemia
Leukemogenesis
Life Sciences
Mutation
Myeloid leukemia
MYH11 gene
Next-generation sequencing
Notch1 protein
Remission
Tyrosine
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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.
ISSN:0026-8933
1608-3245
DOI:10.1134/S0026893320030073