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Deleterious point mutations in T-cell acute lymphoblastic leukemia: Mechanistic insights into leukemogenesis

Roy, U and Raghavan, SC (2021) Deleterious point mutations in T-cell acute lymphoblastic leukemia: Mechanistic insights into leukemogenesis. In: International Journal of Cancer .

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Official URL: https://doi.org/10.1002/ijc.33527


T-cell acute lymphoblastic leukemia (T-ALL) is characterized by the leukemogenic transformation of immature T cells, which accumulate an array of genetic and epigenetic lesions, leading to a sustained proliferation of abnormal T cells. Genetic alterations in the DNA repair genes, protooncogenes, transcription factors, and epigenetic modifiers have been studied in the past decade using next-generation sequencing and high-resolution copy number arrays. While other genomic lesions like chromosomal rearrangements, inversions, insertions, and gene fusions have been well studied at functional level, the mechanism of generation of driver mutations in T-ALL is the subject of current investigation. Novel oncogenic mutations in the TP53, BRCA2, PTEN, IL7R, RAS, NOTCH1, ETV6, BCL11B, WT1, DNMT3A, PRC2, PHF6, USP7, KDM6A and an array of other genes disrupt the genetic and epigenetic homeostasis in T-ALL. In this review, we have summarized the mechanistic role of deleterious driver mutations in T-ALL initiation and progression. We speculate that the formation of non-B DNA structures could be one of the primary reasons for the occurrence of different genomic lesions seen in T-ALL, which warrants further investigation. Understanding the mechanism behind the genesis of oncogenic mutations will pave the way to develop targeted therapies that can improve the overall survival and treatment outcome. © 2021 Union for International Cancer Control.

Item Type: Journal Article
Publication: International Journal of Cancer
Publisher: John Wiley and Sons Inc
Additional Information: The copyright for this article belongs to John Wiley and Sons Inc
Department/Centre: Division of Biological Sciences > Biochemistry
Date Deposited: 07 Jul 2021 06:58
Last Modified: 09 Jul 2021 05:10
URI: http://eprints.iisc.ac.in/id/eprint/68737

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