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Genetic alterations in the DNA repair genes, protooncogenes, transcription factors, and epigenetic modifiers have been studied in the past decade using next\u2010generation sequencing and high\u2010resolution 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\u2010ALL is the subject of current investigation. Novel oncogenic mutations in the <jats:italic>TP53<\/jats:italic>, <jats:italic>BRCA2<\/jats:italic>, <jats:italic>PTEN<\/jats:italic>, <jats:italic>IL7R<\/jats:italic>, <jats:italic>RAS<\/jats:italic>, <jats:italic>NOTCH1<\/jats:italic>, <jats:italic>ETV6<\/jats:italic>, <jats:italic>BCL11B<\/jats:italic>, <jats:italic>WT1<\/jats:italic>, <jats:italic>DNMT3A<\/jats:italic>, <jats:italic>PRC2<\/jats:italic>, <jats:italic>PHF6<\/jats:italic>, <jats:italic>USP7<\/jats:italic>, <jats:italic>KDM6A<\/jats:italic> and an array of other genes disrupt the genetic and epigenetic homeostasis in T\u2010ALL. In this review, we have summarized the mechanistic role of deleterious driver mutations in T\u2010ALL initiation and progression. We speculate that the formation of non\u2010B DNA structures could be one of the primary reasons for the occurrence of different genomic lesions seen in T\u2010ALL, 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.<\/jats:p>","DOI":"10.1002\/ijc.33527","type":"journal-article","created":{"date-parts":[[2021,2,26]],"date-time":"2021-02-26T13:05:02Z","timestamp":1614344702000},"page":"1210-1220","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":25,"title":["Deleterious point mutations in T\u2010cell acute lymphoblastic leukemia: Mechanistic insights into leukemogenesis"],"prefix":"10.1002","volume":"149","author":[{"given":"Urbi","family":"Roy","sequence":"first","affiliation":[{"name":"Department of Biochemistry Indian Institute of Science  Bangalore India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3003-1417","authenticated-orcid":false,"given":"Sathees 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