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Here, we show that ATL can be detected early in HTLV-1-carriers through quantification of T-cell receptor (TCR)V\u03b2 subunit diversity on T-cells infected with HTLV-1 (CD3+ CCR4+ CD26\u2212 T-cells) using an \u2018oligoclonality index\u2019 (OCI-flow). We established a reference range for OCI-flow by analysing peripheral blood mononuclear cells (PBMCs) from HTLV-1-carriers who had not developed ATL in a median of 10.5 years follow up (<jats:italic>n<\/jats:italic>\u2009=\u200938) and patients with ATL (<jats:italic>n<\/jats:italic>\u2009=\u200930). In the third cohort of HTLV-1-carriers with no history or clinical evidence of ATL (<jats:italic>n<\/jats:italic>\u2009=\u2009106), 19% of high proviral load (PVL, \u22654 copies of HTLV-1\/100 PBMCs) carriers had an OCI-flow in the ATL range, &gt;0.770. Carriers with an OCI-flow &gt;0.770 (<jats:italic>n<\/jats:italic>\u2009=\u200914) had higher lymphocyte counts and PVLs and were more likely to have a family history of ATL than carriers with OCI-flow \u22640.770. ATL subsequently developed in two of these 14 carriers but no carriers with OCI-flow \u22640.770 (<jats:italic>p<\/jats:italic>\u2009=\u20090.03, cumulative follow-up 129 person-years). This method can be used to identify a subset of high-PVL HTLV-1-carriers at increased risk of developing ATL who may benefit from intervention therapy, prior to the detection of disease.<\/jats:p>","DOI":"10.1038\/s41408-021-00458-8","type":"journal-article","created":{"date-parts":[[2021,3,26]],"date-time":"2021-03-26T18:02:31Z","timestamp":1616781751000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":29,"title":["Quantification of T cell clonality in human T cell leukaemia virus type-1 carriers can detect the development of adult T cell leukaemia early"],"prefix":"10.1038","volume":"11","author":[{"given":"Sonia N.","family":"Wolf","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jana","family":"Haddow","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claire","family":"Greiller","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Graham P.","family":"Taylor","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lucy B. M.","family":"Cook","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7897-1814","authenticated-orcid":false,"given":"Aileen G.","family":"Rowan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,3,26]]},"reference":[{"key":"458_CR1","doi-asserted-by":"publisher","first-page":"322","DOI":"10.3389\/fmicb.2012.00322","volume":"3","author":"M Iwanaga","year":"2012","unstructured":"Iwanaga, M., Watanabe, T. & Yamaguchi, K. Adult T-cell leukemia: a review of epidemiological evidence. Front. Microbiol. 3, 322 (2012).","journal-title":"Front. Microbiol"},{"key":"458_CR2","doi-asserted-by":"publisher","first-page":"359","DOI":"10.1089\/aid.2012.0132","volume":"29","author":"MA Demontis","year":"2013","unstructured":"Demontis, M. A., Hilburn, S. & Taylor, G. P. Human T cell lymphotropic virus type 1 viral load variability and long-term trends in asymptomatic carriers and in patients with human T cell lymphotropic virus type 1-related diseases. AIDS Res. Hum. Retroviruses 29, 359\u2013364 (2013).","journal-title":"AIDS Res. Hum. Retroviruses"},{"key":"458_CR3","doi-asserted-by":"publisher","first-page":"567","DOI":"10.1002\/cncr.32556","volume":"126","author":"UA Shah","year":"2020","unstructured":"Shah, U. A. et al. Epidemiology and survival trend of adult T-cell leukemia\/lymphoma in the United States. Cancer 126, 567\u2013574 (2020).","journal-title":"Cancer"},{"key":"458_CR4","doi-asserted-by":"publisher","first-page":"51981","DOI":"10.18632\/oncotarget.10223","volume":"7","author":"M Zell","year":"2016","unstructured":"Zell, M. et al. Adult T-cell leukemia\/lymphoma in the Caribbean cohort is a distinct clinical entity with dismal response to conventional chemotherapy. Oncotarget 7, 51981\u201351990 (2016).","journal-title":"Oncotarget"},{"key":"458_CR5","doi-asserted-by":"publisher","first-page":"3488","DOI":"10.1182\/blood-2012-07-445593","volume":"120","author":"LB Cook","year":"2012","unstructured":"Cook, L. B., Rowan, A. G., Melamed, A., Taylor, G. P. & Bangham, C. R. M. HTLV-1-infected T cells contain a single integrated provirus in natural infection. Blood 120, 3488\u20133490 (2012).","journal-title":"Blood"},{"key":"458_CR6","doi-asserted-by":"publisher","first-page":"3925","DOI":"10.1182\/blood-2014-02-553602","volume":"123","author":"LB Cook","year":"2014","unstructured":"Cook, L. B. et al. The role of HTLV-1 clonality, proviral structure, and genomic integration site in adult T-cell leukemia\/lymphoma. Blood 123, 3925\u20133931 (2014).","journal-title":"Blood"},{"key":"458_CR7","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pcbi.1003646","volume":"10","author":"DJ Laydon","year":"2014","unstructured":"Laydon, D. J. et al. 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