{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T04:41:21Z","timestamp":1790138481242,"version":"4.0.1"},"reference-count":107,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2022,5,12]],"date-time":"2022-05-12T00:00:00Z","timestamp":1652313600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Adult T-cell leukemia\/lymphoma (ATLL) is a refractory T-cell neoplasm that develops in human T-cell leukemia virus type-I (HTLV-1) carriers. Large-scale comprehensive genomic analyses have uncovered the landscape of genomic alterations of ATLL and have identified several altered genes related to prognosis. The genetic alterations in ATLL are extremely enriched in the T-cell receptor\/nuclear factor-\u03baB pathway, suggesting a pivotal role of deregulation in this pathway in the transformation of HTLV-1-infected cells. Recent studies have revealed the process of transformation of HTLV-1-infected cells by analyzing longitudinal samples from HTLV-1 carriers and patients with overt ATLL, an endeavor that might enable earlier ATLL diagnosis. The latest whole-genome sequencing study discovered 11 novel alterations, including CIC long isoform, which had been overlooked in previous studies employing exome sequencing. Our study group performed the targeted sequencing of ATLL in Okinawa, the southernmost island in Japan and an endemic area of HTLV-1, where the comprehensive genetic alterations had never been analyzed. We found associations of genetic alterations with HTLV-1 strains phylogenetically classified based on the tax gene, an etiological virus factor in ATLL. This review summarizes the genetic alterations in ATLL, with a focus on their clinical significance, geographical heterogeneity, and association with HTLV-1 strains.<\/jats:p>","DOI":"10.3390\/cancers14102394","type":"journal-article","created":{"date-parts":[[2022,5,12]],"date-time":"2022-05-12T21:46:53Z","timestamp":1652392013000},"page":"2394","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Genetic Alterations in Adult T-Cell Leukemia\/Lymphoma: Novel Discoveries with Clinical and Biological Significance"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2411-2539","authenticated-orcid":false,"given":"Shugo","family":"Sakihama","sequence":"first","affiliation":[{"name":"Department of Pathology and Cell Biology, Graduate School of Medicine, University of the Ryukyus, Nishihara 903-0215, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kennosuke","family":"Karube","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, Graduate School of Medicine, Nagoya University, Nagoya 466-8550, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,5,12]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"481","DOI":"10.1182\/blood.V50.3.481.481","article-title":"Adult T-cell leukemia: Clinical and hematologic features of 16 cases","volume":"50","author":"Uchiyama","year":"1977","journal-title":"Blood"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"7415","DOI":"10.1073\/pnas.77.12.7415","article-title":"Detection and isolation of type C retrovirus particles from fresh and cultured lymphocytes of a patient with cutaneous T-cell lymphoma","volume":"77","author":"Poiesz","year":"1980","journal-title":"Proc. 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