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Approximately 3%\u20135% of infected individuals develop ATL after a prolonged latency of 30\u201350\u00a0years, during which a complex interplay between viral oncoproteins and host genomic alterations drives the transition from viral persistence to overt malignancy. This transformation is orchestrated by the viral transactivator Tax, which initiates cellular transformation, and the HTLV\u20101 basic leucine zipper factor (HBZ), which maintains the malignant phenotype and promotes survival through immune evasion. Genomic profiling has revealed that over 90% of ATL cases harbour activating mutations in the T\u2010cell receptor (TCR)\u2010NF\u2010\u03baB signalling pathway, enabling the malignant clone to bypass viral dependency. Furthermore, ATL cells survive host immunosurveillance through sophisticated escape mechanisms, including the loss of MHC class I presentation and programed death\u2010ligand 1 (PD\u2010L1) overexpression via 3\u2032\u2010untranslated region (UTR) disruption. Despite the use of antiviral therapies and targeted monoclonal antibodies, therapeutic failure is common due to genomic instability\u2014specifically TP53 mutations compromising Zidovudine\/Interferon efficacy and CCR4 antigenic variations leading to mogamulizumab resistance. This review delineates the multi\u2010step journey of HTLV\u20101\u2010driven clonal evolution and evaluates the molecular barriers to effective clinical management.<\/jats:p>","DOI":"10.1002\/rmv.70162","type":"journal-article","created":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T17:54:57Z","timestamp":1777658097000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["HTLV\u20101\u2013Driven Clonal Evolution and Immune Escape in Adult T\u2010Cell Leukaemia: From Viral Persistence to Therapeutic Failure"],"prefix":"10.1002","volume":"36","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7391-0529","authenticated-orcid":false,"given":"Zuhair M.","family":"Mohammedsaleh","sequence":"first","affiliation":[{"name":"Department of Medical Laboratory Technology, Faculty of Applied Medical Sciences University of Tabuk  Tabuk Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-4258-738X","authenticated-orcid":false,"given":"Abdullah F.","family":"Shater","sequence":"additional","affiliation":[{"name":"Department of Medical Laboratory Technology, Faculty of Applied Medical Sciences University of Tabuk  Tabuk Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,5,1]]},"reference":[{"issue":"6","key":"e_1_2_13_2_1","first-page":"485","article-title":"HTLV\u20101 Infection: An Emerging Risk. 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