{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,20]],"date-time":"2026-09-20T21:39:57Z","timestamp":1789940397034,"version":"4.0.1"},"reference-count":19,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2006,7,18]],"date-time":"2006-07-18T00:00:00Z","timestamp":1153180800000},"content-version":"vor","delay-in-days":4142,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Intl Journal of Cancer"],"published-print":{"date-parts":[[1995,3,16]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Adult T\u2010cell leukemia\/lymphoma (ATL) usually develops after age 40 in Japan, suggesting a long latency since HTLV\u2010I is considered to be transmitted mainly from mothers to babies via breast milk. Our previous studies had suggested that HTLV\u2010I carriers who have a monoclonal integration of HTLV\u2010I proviral DNA in the peripheral blood cells, designated pre\u2010ATL, account for about 2% of healthy carriers and are at high risk of developing ATL Their ages ranged from 32 to 80 (median 57). Nevertheless, many cases of pre\u2010ATL showed a long\u2010lasting carrier state (10\u2010year probability around 90%). In the present investigation we conducted a large\u2010scale molecular detection of monoclonal integration in a population (481 cases) of healthy carriers with ages ranging from 16 to 82 (median 49) for the purpose of clarifying the earliest onset of this pre\u2010ATL state. Southern\u2010blot analysis of DNA extracted from peripheral blood mononuclear cells revealed 6 cases (1.2%) with a monoclonal band. All of these 6 were older than 40; no single positive case was found in 220 carriers under age 40. These results indicate that the molecularly detectable pre\u2010ATL state also develops after a long latency. Thus the pre\u2010ATL state seems to be a subtype of ATL showing an extremely indolent course of disease development, but not merely an early phase of all subtypes of ATL. We propose that, in order to reveal a promoter(s) responsible for the development of ATL from the pre\u2010ATL state, intensive epidemiological investigation of life style, eating habits, occupation and exposure to carcinogens must be conducted on this unique group prone to ATL. It is also important to perform such an epidemiological study on the general population of carriers by paying special attention to the first 3\u20104 decades of each carrier's life in Japan and by comparing the data with those from carriers in different geographical areas of the world.<\/jats:p>","DOI":"10.1002\/ijc.2910600612","type":"journal-article","created":{"date-parts":[[2007,2,20]],"date-time":"2007-02-20T00:38:49Z","timestamp":1171931929000},"page":"798-801","source":"Crossref","is-referenced-by-count":11,"title":["Molecular detection of pre\u2010atl state among healthy HTLV\u20101 carriers in an endemic area of Japan"],"prefix":"10.1002","volume":"60","author":[{"given":"Yun\u2010Xian","family":"Ghen","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuichi","family":"Jkeda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroyuki","family":"Mori","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomoko","family":"Hata","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kunihiro","family":"Tsukasaki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saburo","family":"Momita","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasuaki","family":"Yamada","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shimeru","family":"Kamihira","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mariko","family":"Mine","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masao","family":"Tomonaga","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2006,7,18]]},"reference":[{"key":"e_1_2_1_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.2910300302"},{"key":"e_1_2_1_3_1","first-page":"694","article-title":"Retroviruses and cencer: US\u2010Japan Clinico\u2010epidemiological experiences","volume":"8","author":"Greavws W. 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Prevent."},{"key":"e_1_2_1_7_1","doi-asserted-by":"crossref","first-page":"2017","DOI":"10.1182\/blood.V82.7.2017.2017","article-title":"Clinical course of human T\u2010lymphotropic virus type 1 carriers with molecularly detectable monoclonal proliferation of T lymphocytes: defining a low\u2010 and high\u2010risk population","volume":"82","author":"Ikeda S.","year":"1993","journal-title":"Blood"},{"key":"e_1_2_1_8_1","doi-asserted-by":"crossref","first-page":"120","DOI":"10.1182\/blood.V66.1.120.120","article-title":"Preleukemie state of adult T cell leukemia: abnormal T lymphocytosis induced by human adult T cell leukemialymphoma virus","volume":"66","author":"Kinoshita K.","year":"1985","journal-title":"Blood"},{"key":"e_1_2_1_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.2910430618"},{"key":"e_1_2_1_10_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1349-7006.1989.tb02289.x"},{"key":"e_1_2_1_11_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.77.12.7415"},{"key":"e_1_2_1_12_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2141.1991.tb08051.x"},{"key":"e_1_2_1_13_1","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.2910400605"},{"key":"e_1_2_1_14_1","first-page":"423","article-title":"Estimation of rate of incidence of ATL among ATLV (HTLV\u2010I) carriers in Kyushu, Japan. Zap","volume":"15","author":"Tajima K.","year":"1985","journal-title":"J. clin. Oncol."},{"key":"e_1_2_1_15_1","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.2910450206"},{"key":"e_1_2_1_16_1","first-page":"495","article-title":"Geographical features and epidemiological approach to endemic T\u2010cell leukemia\/lymphoma in Japan","volume":"9","author":"Tajima K.","year":"1979","journal-title":"Jpn. J. Clin. Oncol."},{"key":"e_1_2_1_17_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V50.3.481.481"},{"key":"e_1_2_1_18_1","doi-asserted-by":"crossref","unstructured":"Yamaguchi K. Matutes E. Catovsky D. Galton D. A. G. Nakada K.andTakatsuki K. Strongyloides stercoralis as candidate co\u2010factor for HTLV\u2010I\u2010induced leukemogenesis. The Lancet 94\u201395(1987).","DOI":"10.1016\/S0140-6736(87)92752-8"},{"key":"e_1_2_1_19_1","first-page":"217","article-title":"Positive and negative regulation of HTLV\u2010I gene expression and their roles in leukemogenesis in ATL. 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