{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T23:06:35Z","timestamp":1792710395215,"version":"4.5.0"},"reference-count":35,"publisher":"National Academy of Sciences","issue":"21","license":[{"start":{"date-parts":[[2020,5,11]],"date-time":"2020-05-11T00:00:00Z","timestamp":1589155200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003478","name":"Ministry of Health, Labour and Welfare","doi-asserted-by":"publisher","award":["H28-nanchi-ippan-018"],"award-info":[{"award-number":["H28-nanchi-ippan-018"]}],"id":[{"id":"10.13039\/501100003478","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003478","name":"Ministry of Health, Labour and Welfare","doi-asserted-by":"publisher","award":["19FC1007"],"award-info":[{"award-number":["19FC1007"]}],"id":[{"id":"10.13039\/501100003478","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009619","name":"Japan Agency for Medical Research and Development","doi-asserted-by":"publisher","award":["JP19ek0109356"],"award-info":[{"award-number":["JP19ek0109356"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009619","name":"Japan Agency for Medical Research and Development","doi-asserted-by":"publisher","award":["JP19ek0109346"],"award-info":[{"award-number":["JP19ek0109346"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009619","name":"Japan Agency for Medical Research and Development","doi-asserted-by":"publisher","award":["JP19fk010839"],"award-info":[{"award-number":["JP19fk010839"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009619","name":"Japan Agency for Medical Research and Development","doi-asserted-by":"publisher","award":["JP19ak0101086"],"award-info":[{"award-number":["JP19ak0101086"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009619","name":"Japan Agency for Medical Research and Development","doi-asserted-by":"publisher","award":["JP19ck0106256"],"award-info":[{"award-number":["JP19ck0106256"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"MEXT | Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["19H03575"],"award-info":[{"award-number":["19H03575"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"MEXT | Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["18K08317"],"award-info":[{"award-number":["18K08317"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2020,5,26]]},"abstract":"<jats:p>Human T cell leukemia virus 1 (HTLV-1) causes the functionally debilitating disease HTLV-1\u2013associated myelopathy\/tropical spastic paraparesis (HAM\/TSP) as well as adult T cell leukemia lymphoma (ATLL). Although there were concerns that the mortality of HAM\/TSP could be affected by the development of ATLL, prospective evidence was lacking in this area. In this 5-y prospective cohort study, we determined the mortality, prevalence, and incidence of ATLL in 527 HAM\/TSP patients. The standard mortality ratio of HAM\/TSP patients was 2.25, and ATLL was one of the major causes of death (5\/33 deaths). ATLL prevalence and incidence in these patients were 3.0% and 3.81 per 1,000 person-y, respectively. To identify patients at a high risk of developing ATLL, flow cytometry, Southern blotting, and targeted sequencing data were analyzed in a separate cohort of 218 HAM\/TSP patients. In 17% of the HAM\/TSP patients, we identified an increase in T cells positive for cell adhesion molecule 1 (CADM1), a marker for ATLL and HTLV-1\u2013infected cells. Genomic analysis revealed that somatic mutations of HTLV-1\u2013infected cells were seen in 90% of these cases and 11% of them had dominant clone and developed ATLL in the longitudinal observation. In this study, we were able to demonstrate the increased mortality in patients with HAM\/TSP and a significant effect of ATLL on their prognosis. Having dominant clonal expansion of HTLV-1\u2013infected cells with ATLL-associated somatic mutations may be important characteristics of patients with HAM\/TSP who are at an increased risk of developing ATLL.<\/jats:p>","DOI":"10.1073\/pnas.1920346117","type":"journal-article","created":{"date-parts":[[2020,5,11]],"date-time":"2020-05-11T20:25:55Z","timestamp":1589228755000},"page":"11685-11691","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":46,"title":["Mortality and risk of progression to adult T cell leukemia\/lymphoma in HTLV-1\u2013associated myelopathy\/tropical spastic paraparesis"],"prefix":"10.1073","volume":"117","author":[{"given":"Misako","family":"Nagasaka","sequence":"first","affiliation":[{"name":"Division of Neurology, Department of Internal Medicine, St. Marianna University School of Medicine, Kawasaki, Kanagawa 216\u20108511, Japan;"},{"name":"Department of Oncology, Karmanos Cancer Institute, Detroit, MI 48201;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Makoto","family":"Yamagishi","sequence":"additional","affiliation":[{"name":"Department of Computational Biology and Medical Sciences, Graduate School of Frontier Sciences, The University of Tokyo, Minato-ku, Tokyo 108-8639, Japan;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naoko","family":"Yagishita","sequence":"additional","affiliation":[{"name":"Department of Rare Diseases Research, Institute of Medical Science, St. Marianna University School of Medicine, Kawasaki, Kanagawa 216\u20108512, Japan;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natsumi","family":"Araya","sequence":"additional","affiliation":[{"name":"Department of Rare Diseases Research, Institute of Medical Science, St. Marianna University School of Medicine, Kawasaki, Kanagawa 216\u20108512, Japan;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seiichiro","family":"Kobayashi","sequence":"additional","affiliation":[{"name":"Division of Molecular Therapy, The Institute of Medical Science, The University of Tokyo, Tokyo 108-8639, Japan;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0883-2920","authenticated-orcid":false,"given":"Junya","family":"Makiyama","sequence":"additional","affiliation":[{"name":"Department of Hematology\/Oncology, Research Hospital, The Institute of Medical Science, The University of Tokyo, Tokyo 108-8639, Japan;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miyuki","family":"Kubokawa","sequence":"additional","affiliation":[{"name":"Department of Computational Biology and Medical Sciences, Graduate School of Frontier Sciences, The University of Tokyo, Minato-ku, Tokyo 108-8639, Japan;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junji","family":"Yamauchi","sequence":"additional","affiliation":[{"name":"Department of Rare Diseases Research, Institute of Medical Science, St. Marianna University School of Medicine, Kawasaki, Kanagawa 216\u20108512, Japan;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0292-1594","authenticated-orcid":false,"given":"Daisuke","family":"Hasegawa","sequence":"additional","affiliation":[{"name":"Department of Rare Diseases Research, Institute of Medical Science, St. Marianna University School of Medicine, Kawasaki, Kanagawa 216\u20108512, Japan;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8549-6559","authenticated-orcid":false,"given":"Ariella L. G.","family":"Coler-Reilly","sequence":"additional","affiliation":[{"name":"Department of Rare Diseases Research, Institute of Medical Science, St. Marianna University School of Medicine, Kawasaki, Kanagawa 216\u20108512, Japan;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuntaro","family":"Tsutsumi","sequence":"additional","affiliation":[{"name":"Division of Neurology, Department of Internal Medicine, St. Marianna University School of Medicine, Kawasaki, Kanagawa 216\u20108511, Japan;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Uemura","sequence":"additional","affiliation":[{"name":"Division of Hematology and Oncology, Department of Internal Medicine, St. Marianna University School of Medicine, Kawasaki, Kanagawa 216\u20108511, Japan;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ayako","family":"Arai","sequence":"additional","affiliation":[{"name":"Division of Hematology and Oncology, Department of Internal Medicine, St. Marianna University School of Medicine, Kawasaki, Kanagawa 216\u20108511, Japan;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ayako","family":"Takata","sequence":"additional","affiliation":[{"name":"Department of Preventive Medicine, St. Marianna University School of Medicine, Kawasaki, Kanagawa 216\u20108511, Japan;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eisuke","family":"Inoue","sequence":"additional","affiliation":[{"name":"Department of Medical Informatics, St. Marianna University School of Medicine, Kawasaki, Kanagawa 216\u20108511, Japan;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3200-376X","authenticated-orcid":false,"given":"Yasuhiro","family":"Hasegawa","sequence":"additional","affiliation":[{"name":"Division of Neurology, Department of Internal Medicine, St. Marianna University School of Medicine, Kawasaki, Kanagawa 216\u20108511, Japan;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toshiki","family":"Watanabe","sequence":"additional","affiliation":[{"name":"Department of Hematology\/Oncology, Research Hospital, The Institute of Medical Science, The University of Tokyo, Tokyo 108-8639, Japan;"},{"name":"Department of Practical Management of Medical Information, St. Marianna University Graduate School of Medicine, Kawasaki, Kanagawa 216-8512, Japan;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yutaka","family":"Suzuki","sequence":"additional","affiliation":[{"name":"Department of Computational Biology and Medical Sciences, Graduate School of Frontier Sciences, The University of Tokyo, Chiba 277-8561, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kaoru","family":"Uchimaru","sequence":"additional","affiliation":[{"name":"Department of Computational Biology and Medical Sciences, Graduate School of Frontier Sciences, The University of Tokyo, Minato-ku, Tokyo 108-8639, Japan;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomoo","family":"Sato","sequence":"additional","affiliation":[{"name":"Department of Rare Diseases Research, Institute of Medical Science, St. Marianna University School of Medicine, Kawasaki, Kanagawa 216\u20108512, Japan;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7527-0345","authenticated-orcid":false,"given":"Yoshihisa","family":"Yamano","sequence":"additional","affiliation":[{"name":"Division of Neurology, Department of Internal Medicine, St. Marianna University School of Medicine, Kawasaki, Kanagawa 216\u20108511, Japan;"},{"name":"Department of Rare Diseases Research, Institute of Medical Science, St. Marianna University School of Medicine, Kawasaki, Kanagawa 216\u20108512, Japan;"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2020,5,11]]},"reference":[{"key":"e_1_3_4_1_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 B. J.","year":"1980","unstructured":"B. J. Poiesz ., Detection and isolation of type C retrovirus particles from fresh and cultured lymphocytes of a patient with cutaneous T-cell lymphoma. Proc. Natl. Acad. Sci. U.S.A. 77, 7415\u20137419 (1980).","journal-title":"Proc. Natl. Acad. Sci. U.S.A."},{"key":"e_1_3_4_2_2","doi-asserted-by":"crossref","first-page":"388","DOI":"10.3389\/fmicb.2012.00388","article-title":"Epidemiological aspects and world distribution of HTLV-1 infection","volume":"3","author":"Gessain A.","year":"2012","unstructured":"A. Gessain, O. Cassar, Epidemiological aspects and world distribution of HTLV-1 infection. Front. Microbiol. 3, 388 (2012).","journal-title":"Front. Microbiol."},{"key":"e_1_3_4_3_2","doi-asserted-by":"crossref","first-page":"1031","DOI":"10.1016\/S0140-6736(86)91298-5","article-title":"HTLV-I associated myelopathy, a new clinical entity","volume":"1","author":"Osame M.","year":"1986","unstructured":"M. Osame ., HTLV-I associated myelopathy, a new clinical entity. Lancet 1, 1031\u20131032 (1986).","journal-title":"Lancet"},{"key":"e_1_3_4_4_2","doi-asserted-by":"crossref","first-page":"407","DOI":"10.1016\/S0140-6736(85)92734-5","article-title":"Antibodies to human T-lymphotropic virus type-I in patients with tropical spastic paraparesis","volume":"2","author":"Gessain A.","year":"1985","unstructured":"A. Gessain ., Antibodies to human T-lymphotropic virus type-I in patients with tropical spastic paraparesis. Lancet 2, 407\u2013410 (1985).","journal-title":"Lancet"},{"key":"e_1_3_4_5_2","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 T.","year":"1977","unstructured":"T. Uchiyama, J. Yodoi, K. Sagawa, K. Takatsuki, H. Uchino, Adult T-cell leukemia: Clinical and hematologic features of 16 cases. Blood 50, 481\u2013492 (1977).","journal-title":"Blood"},{"key":"e_1_3_4_6_2","doi-asserted-by":"crossref","first-page":"F1000 Faculty R","DOI":"10.12688\/f1000research.17479.1","article-title":"40 years of the human T-cell leukemia virus: Past, present and future","volume":"8","author":"Tagaya Y.","year":"2019","unstructured":"Y. Tagaya, M. Matsuoka, R. Gallo, 40 years of the human T-cell leukemia virus: Past, present and future. F1000Res. 8, F1000 Faculty Rev 228 (2019).","journal-title":"F1000Res."},{"key":"e_1_3_4_7_2","doi-asserted-by":"crossref","first-page":"1893","DOI":"10.1016\/S0140-6736(18)30974-7","article-title":"Time to eradicate HTLV-1: An open letter to WHO","volume":"391","author":"Martin F.","year":"2018","unstructured":"F. Martin, Y. Tagaya, R. Gallo, Time to eradicate HTLV-1: An open letter to WHO. Lancet 391, 1893\u20131894 (2018).","journal-title":"Lancet"},{"key":"e_1_3_4_8_2","volume-title":"WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues","author":"Swerdlow S. H.","year":"2008","unstructured":"S. H. Swerdlow ., WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues (IARC, Lyon, France, 2008)."},{"key":"e_1_3_4_9_2","doi-asserted-by":"crossref","first-page":"2570","DOI":"10.1182\/blood-2015-03-632489","article-title":"Treatment and survival among 1594 patients with ATL","volume":"126","author":"Katsuya H.","year":"2015","unstructured":"H. Katsuya .; ATL-Prognostic Index Project, Treatment and survival among 1594 patients with ATL. Blood 126, 2570\u20132577 (2015).","journal-title":"Blood"},{"key":"e_1_3_4_10_2","doi-asserted-by":"crossref","first-page":"15012","DOI":"10.1038\/nrdp.2015.12","article-title":"HTLV-1-associated myelopathy\/tropical spastic paraparesis","volume":"1","author":"Bangham C. R.","year":"2015","unstructured":"C. R. Bangham, A. Araujo, Y. Yamano, G. P. Taylor, HTLV-1-associated myelopathy\/tropical spastic paraparesis. Nat. Rev. Dis. Primers 1, 15012 (2015).","journal-title":"Nat. Rev. Dis. Primers"},{"key":"e_1_3_4_11_2","doi-asserted-by":"crossref","first-page":"466","DOI":"10.1097\/00042560-199504120-00006","article-title":"Clinical spectrum of HTLV-I in south Florida","volume":"8","author":"Harrington W. J.","year":"1995","unstructured":"W. J. Harrington, Jr ., Clinical spectrum of HTLV-I in south Florida. J. Acquir. Immune Defic. Syndr. Hum. Retrovirol. 8, 466\u2013473 (1995).","journal-title":"J. Acquir. Immune Defic. Syndr. Hum. Retrovirol."},{"key":"e_1_3_4_12_2","doi-asserted-by":"crossref","first-page":"1336","DOI":"10.1136\/jnnp.2009.191239","article-title":"A 15-year prospective longitudinal study of disease progression in patients with HTLV-1 associated myelopathy in the UK","volume":"81","author":"Martin F.","year":"2010","unstructured":"F. Martin, A. Fedina, S. Youshya, G. P. Taylor, A 15-year prospective longitudinal study of disease progression in patients with HTLV-1 associated myelopathy in the UK. J. Neurol. Neurosurg. Psychiatry 81, 1336\u20131340 (2010).","journal-title":"J. Neurol. Neurosurg. Psychiatry"},{"key":"e_1_3_4_13_2","doi-asserted-by":"crossref","first-page":"336","DOI":"10.1258\/0956462991914078","article-title":"Simultaneous occurrence of HTLV-I associated myelopathy, uveitis and smouldering adult T cell leukaemia. GIPH (Interdisciplinary HTLV-I\/II Research Group)","volume":"10","author":"Gon\u00e7alves D. U.","year":"1999","unstructured":"D. U. Gon\u00e7alves ., Simultaneous occurrence of HTLV-I associated myelopathy, uveitis and smouldering adult T cell leukaemia. GIPH (Interdisciplinary HTLV-I\/II Research Group). Int. J. STD AIDS 10, 336\u2013337 (1999).","journal-title":"Int. J. STD AIDS"},{"key":"e_1_3_4_14_2","doi-asserted-by":"crossref","first-page":"1211","DOI":"10.1182\/blood-2009-12-257410","article-title":"Human T-cell leukemia virus type I (HTLV-1) proviral load and disease progression in asymptomatic HTLV-1 carriers: A nationwide prospective study in Japan","volume":"116","author":"Iwanaga M.","year":"2010","unstructured":"M. Iwanaga .; Joint Study on Predisposing Factors of ATL Development Investigators, Human T-cell leukemia virus type I (HTLV-1) proviral load and disease progression in asymptomatic HTLV-1 carriers: A nationwide prospective study in Japan. Blood 116, 1211\u20131219 (2010).","journal-title":"Blood"},{"key":"e_1_3_4_15_2","doi-asserted-by":"crossref","first-page":"1195","DOI":"10.1182\/bloodadvances.2017005900","article-title":"Clonality of HTLV-1-infected T cells as a risk indicator for development and progression of adult T-cell leukemia","volume":"1","author":"Firouzi S.","year":"2017","unstructured":"S. Firouzi ., Clonality of HTLV-1-infected T cells as a risk indicator for development and progression of adult T-cell leukemia. Blood Adv. 1, 1195\u20131205 (2017).","journal-title":"Blood Adv."},{"key":"e_1_3_4_16_2","doi-asserted-by":"crossref","first-page":"586","DOI":"10.3109\/13550289809114225","article-title":"Analysis of HTLV-I proviral load in 202 HAM\/TSP patients and 243 asymptomatic HTLV-I carriers: High proviral load strongly predisposes to HAM\/TSP","volume":"4","author":"Nagai M.","year":"1998","unstructured":"M. Nagai ., Analysis of HTLV-I proviral load in 202 HAM\/TSP patients and 243 asymptomatic HTLV-I carriers: High proviral load strongly predisposes to HAM\/TSP. J. Neurovirol. 4, 586\u2013593 (1998).","journal-title":"J. Neurovirol."},{"key":"e_1_3_4_17_2","doi-asserted-by":"crossref","first-page":"1304","DOI":"10.1038\/ng.3415","article-title":"Integrated molecular analysis of adult T cell leukemia\/lymphoma","volume":"47","author":"Kataoka K.","year":"2015","unstructured":"K. Kataoka ., Integrated molecular analysis of adult T cell leukemia\/lymphoma. Nat. Genet. 47, 1304\u20131315 (2015).","journal-title":"Nat. Genet."},{"key":"e_1_3_4_18_2","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1186\/s13023-016-0451-x","article-title":"Nation-wide epidemiological study of Japanese patients with rare viral myelopathy using novel registration system (HAM-net)","volume":"11","author":"Coler-Reilly A. L. G.","year":"2016","unstructured":"A. L. G. Coler-Reilly ., Nation-wide epidemiological study of Japanese patients with rare viral myelopathy using novel registration system (HAM-net). Orphanet J. Rare Dis. 11, 69 (2016).","journal-title":"Orphanet J. Rare Dis."},{"key":"e_1_3_4_19_2","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1182\/blood.V99.1.88","article-title":"Correlation of human T-cell lymphotropic virus type 1 (HTLV-1) mRNA with proviral DNA load, virus-specific CD8+ T cells, and disease severity in HTLV-1-associated myelopathy (HAM\/TSP)","volume":"99","author":"Yamano Y.","year":"2002","unstructured":"Y. Yamano ., Correlation of human T-cell lymphotropic virus type 1 (HTLV-1) mRNA with proviral DNA load, virus-specific CD8+ T cells, and disease severity in HTLV-1-associated myelopathy (HAM\/TSP). Blood 99, 88\u201394 (2002).","journal-title":"Blood"},{"key":"e_1_3_4_20_2","doi-asserted-by":"crossref","first-page":"673","DOI":"10.1111\/1348-0421.12644","article-title":"Development of reference material with assigned value for human T-cell leukemia virus type 1 quantitative PCR in Japan","volume":"62","author":"Kuramitsu M.","year":"2018","unstructured":"M. Kuramitsu ., Development of reference material with assigned value for human T-cell leukemia virus type 1 quantitative PCR in Japan. Microbiol. Immunol. 62, 673\u2013676 (2018).","journal-title":"Microbiol. Immunol."},{"key":"e_1_3_4_21_2","doi-asserted-by":"crossref","first-page":"529","DOI":"10.1056\/NEJMoa1704827","article-title":"Mogamulizumab (Anti-CCR4) in HTLV-1-associated myelopathy","volume":"378","author":"Sato T.","year":"2018","unstructured":"T. Sato ., Mogamulizumab (Anti-CCR4) in HTLV-1-associated myelopathy. N. Engl. J. Med. 378, 529\u2013538 (2018).","journal-title":"N. Engl. J. Med."},{"key":"e_1_3_4_22_2","doi-asserted-by":"crossref","first-page":"598","DOI":"10.1111\/cas.12639","article-title":"Advanced human T-cell leukemia virus type 1 carriers and early-stage indolent adult T-cell leukemia-lymphoma are indistinguishable based on CADM1 positivity in flow cytometry","volume":"106","author":"Kobayashi S.","year":"2015","unstructured":"S. Kobayashi ., Advanced human T-cell leukemia virus type 1 carriers and early-stage indolent adult T-cell leukemia-lymphoma are indistinguishable based on CADM1 positivity in flow cytometry. Cancer Sci. 106, 598\u2013603 (2015).","journal-title":"Cancer Sci."},{"key":"e_1_3_4_23_2","doi-asserted-by":"crossref","first-page":"2851","DOI":"10.1158\/1078-0432.CCR-13-3169","article-title":"CADM1 expression and stepwise downregulation of CD7 are closely associated with clonal expansion of HTLV-I-infected cells in adult T-cell leukemia\/lymphoma","volume":"20","author":"Kobayashi S.","year":"2014","unstructured":"S. Kobayashi ., CADM1 expression and stepwise downregulation of CD7 are closely associated with clonal expansion of HTLV-I-infected cells in adult T-cell leukemia\/lymphoma. Clin. Cancer Res. 20, 2851\u20132861 (2014).","journal-title":"Clin. Cancer Res."},{"key":"e_1_3_4_24_2","doi-asserted-by":"crossref","first-page":"1085","DOI":"10.1016\/S0140-6736(87)90506-X","article-title":"Viruses detected in HTLV-I-associated myelopathy and adult T-cell leukaemia are identical on DNA blotting","volume":"1","author":"Yoshida M.","year":"1987","unstructured":"M. Yoshida, M. Osame, K. Usuku, M. Matsumoto, A. Igata, Viruses detected in HTLV-I-associated myelopathy and adult T-cell leukaemia are identical on DNA blotting. Lancet 1, 1085\u20131086 (1987).","journal-title":"Lancet"},{"key":"e_1_3_4_25_2","doi-asserted-by":"crossref","first-page":"696","DOI":"10.1038\/s41568-018-0060-1","article-title":"The COSMIC cancer gene census: Describing genetic dysfunction across all human cancers","volume":"18","author":"Sondka Z.","year":"2018","unstructured":"Z. Sondka ., The COSMIC cancer gene census: Describing genetic dysfunction across all human cancers. Nat. Rev. Cancer 18, 696\u2013705 (2018).","journal-title":"Nat. Rev. Cancer"},{"key":"e_1_3_4_26_2","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1016\/j.ccr.2011.12.015","article-title":"Polycomb-mediated loss of miR-31 activates NIK-dependent NF-\u03baB pathway in adult T cell leukemia and other cancers","volume":"21","author":"Yamagishi M.","year":"2012","unstructured":"M. Yamagishi ., Polycomb-mediated loss of miR-31 activates NIK-dependent NF-\u03baB pathway in adult T cell leukemia and other cancers. Cancer Cell 21, 121\u2013135 (2012).","journal-title":"Cancer Cell"},{"key":"e_1_3_4_27_2","doi-asserted-by":"crossref","first-page":"2078","DOI":"10.1093\/bioinformatics\/btp352","article-title":"The sequence alignment\/map (SAM) format and SAMtools","volume":"25","author":"Li H.","year":"2009","unstructured":"H. Li .; 1000 Genome Project Data Processing Subgroup, The sequence alignment\/map (SAM) format and SAMtools. Bioinformatics 25, 2078\u20132079 (2009).","journal-title":"Bioinformatics"},{"key":"e_1_3_4_28_2","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1038\/nbt.2514","article-title":"Sensitive detection of somatic point mutations in impure and heterogeneous cancer samples","volume":"31","author":"Cibulskis K.","year":"2013","unstructured":"K. Cibulskis ., Sensitive detection of somatic point mutations in impure and heterogeneous cancer samples. Nat. Biotechnol. 31, 213\u2013219 (2013).","journal-title":"Nat. Biotechnol."},{"key":"e_1_3_4_29_2","doi-asserted-by":"crossref","first-page":"e164","DOI":"10.1093\/nar\/gkq603","article-title":"ANNOVAR: Functional annotation of genetic variants from high-throughput sequencing data","volume":"38","author":"Wang K.","year":"2010","unstructured":"K. Wang, M. Li, H. Hakonarson, ANNOVAR: Functional annotation of genetic variants from high-throughput sequencing data. Nucleic Acids Res. 38, e164 (2010).","journal-title":"Nucleic Acids Res."},{"key":"e_1_3_4_30_2","doi-asserted-by":"crossref","first-page":"324","DOI":"10.1136\/jnnp-2015-310361","article-title":"Mortality in multiple sclerosis: Meta-analysis of standardised mortality ratios","volume":"87","author":"Manouchehrinia A.","year":"2016","unstructured":"A. Manouchehrinia, R. Tanasescu, C. R. Tench, C. S. Constantinescu, Mortality in multiple sclerosis: Meta-analysis of standardised mortality ratios. J. Neurol. Neurosurg. Psychiatry 87, 324\u2013331 (2016).","journal-title":"J. Neurol. Neurosurg. Psychiatry"},{"key":"e_1_3_4_31_2","doi-asserted-by":"crossref","first-page":"E25","DOI":"10.3390\/pathogens9010025","article-title":"Dichotomy in fatal outcomes in a large cohort of people living with HTLV-1 in S\u00e3o Paulo, Brazil","volume":"9","author":"Marcusso R. M. N.","year":"2019","unstructured":"R. M. N. Marcusso ., Dichotomy in fatal outcomes in a large cohort of people living with HTLV-1 in S\u00e3o Paulo, Brazil. Pathogens 9, E25 (2019).","journal-title":"Pathogens"},{"key":"e_1_3_4_32_2","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1002\/(SICI)1097-0215(20000201)85:3<319::AID-IJC4>3.0.CO;2-B","article-title":"Evaluation of adult T-cell leukemia\/lymphoma incidence and its impact on non-Hodgkin lymphoma incidence in southwestern Japan","volume":"85","author":"Arisawa K.","year":"2000","unstructured":"K. Arisawa ., Evaluation of adult T-cell leukemia\/lymphoma incidence and its impact on non-Hodgkin lymphoma incidence in southwestern Japan. Int. J. Cancer 85, 319\u2013324 (2000).","journal-title":"Int. J. Cancer"},{"key":"e_1_3_4_33_2","doi-asserted-by":"crossref","first-page":"3746","DOI":"10.1111\/cas.14219","article-title":"CD4+ CADM1+ cell percentage predicts disease progression in HTLV-1 carriers and indolent adult T-cell leukemia\/lymphoma","volume":"110","author":"Makiyama J.","year":"2019","unstructured":"J. Makiyama ., CD4+ CADM1+ cell percentage predicts disease progression in HTLV-1 carriers and indolent adult T-cell leukemia\/lymphoma. Cancer Sci. 110, 3746\u20133753 (2019).","journal-title":"Cancer Sci."},{"key":"e_1_3_4_34_2","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1182\/blood-2017-01-761874","article-title":"Prognostic relevance of integrated genetic profiling in adult T-cell leukemia\/lymphoma","volume":"131","author":"Kataoka K.","year":"2018","unstructured":"K. Kataoka ., Prognostic relevance of integrated genetic profiling in adult T-cell leukemia\/lymphoma. Blood 131, 215\u2013225 (2018).","journal-title":"Blood"},{"key":"e_1_3_4_35_2","doi-asserted-by":"crossref","first-page":"7529","DOI":"10.1158\/1078-0432.CCR-04-0983","article-title":"The CC chemokine receptor 4 as a novel specific molecular target for immunotherapy in adult T-cell leukemia\/lymphoma","volume":"10","author":"Ishida T.","year":"2004","unstructured":"T. Ishida ., The CC chemokine receptor 4 as a novel specific molecular target for immunotherapy in adult T-cell leukemia\/lymphoma. Clin. Cancer Res. 10, 7529\u20137539 (2004).","journal-title":"Clin. Cancer Res."}],"container-title":["Proceedings of the National Academy of Sciences"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/www.pnas.org\/syndication\/doi\/10.1073\/pnas.1920346117","content-type":"unspecified","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/pnas.org\/doi\/pdf\/10.1073\/pnas.1920346117","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,6,7]],"date-time":"2022-06-07T18:29:14Z","timestamp":1654626554000},"score":1,"resource":{"primary":{"URL":"https:\/\/pnas.org\/doi\/full\/10.1073\/pnas.1920346117"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,5,11]]},"references-count":35,"journal-issue":{"issue":"21","published-print":{"date-parts":[[2020,5,26]]}},"alternative-id":["10.1073\/pnas.1920346117"],"URL":"https:\/\/doi.org\/10.1073\/pnas.1920346117","relation":{},"ISSN":["0027-8424","1091-6490"],"issn-type":[{"value":"0027-8424","type":"print"},{"value":"1091-6490","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,5,11]]},"assertion":[{"value":"2020-05-11","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}