{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,19]],"date-time":"2026-09-19T21:10:06Z","timestamp":1789852206375,"version":"4.0.1"},"reference-count":19,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2016,6,22]],"date-time":"2016-06-22T00:00:00Z","timestamp":1466553600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/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":["H26\u2010Kakushingann\u2010Ippan\u2010010"],"award-info":[{"award-number":["H26\u2010Kakushingann\u2010Ippan\u2010010"]}],"id":[{"id":"10.13039\/501100003478","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancer Science"],"published-print":{"date-parts":[[2016,8]]},"abstract":"<jats:p>Adult T\u2010cell leukemia\/lymphoma (<jats:styled-content style=\"fixed-case\">ATL<\/jats:styled-content>) develops in human T\u2010cell leukemia virus type 1 (<jats:styled-content style=\"fixed-case\">HTLV<\/jats:styled-content>\u20101) carriers. Although the <jats:styled-content style=\"fixed-case\">HTLV<\/jats:styled-content>\u20101\u2010encoded <jats:italic><jats:styled-content style=\"fixed-case\">HBZ<\/jats:styled-content><\/jats:italic> gene is critically involved, <jats:italic><jats:styled-content style=\"fixed-case\">HBZ<\/jats:styled-content><\/jats:italic> alone is insufficient and additional, cooperative \u201chits\u201d are required for the development of <jats:styled-content style=\"fixed-case\">ATL<\/jats:styled-content>. Candidate cooperative hits are being defined, but methods to rapidly explore their roles in <jats:styled-content style=\"fixed-case\">ATL<\/jats:styled-content> development in collaboration with <jats:italic><jats:styled-content style=\"fixed-case\">HBZ<\/jats:styled-content><\/jats:italic> are lacking. Here, we present a new mouse model of acute type <jats:styled-content style=\"fixed-case\">ATL<\/jats:styled-content> that can be generated rapidly by transplanting <jats:italic>in\u00a0vitro<\/jats:italic>\u2010induced T cells that have been retrovirally transduced with <jats:italic><jats:styled-content style=\"fixed-case\">HBZ<\/jats:styled-content><\/jats:italic> and two cooperative genes, <jats:italic><jats:styled-content style=\"fixed-case\">BCL<\/jats:styled-content>xL<\/jats:italic> and <jats:italic><jats:styled-content style=\"fixed-case\">AKT<\/jats:styled-content><\/jats:italic>, into mice. Co\u2010transduction of <jats:italic><jats:styled-content style=\"fixed-case\">HBZ<\/jats:styled-content><\/jats:italic> and <jats:italic><jats:styled-content style=\"fixed-case\">BCL<\/jats:styled-content>xL<\/jats:italic>\/<jats:italic><jats:styled-content style=\"fixed-case\">AKT<\/jats:styled-content><\/jats:italic> allowed these T cells to grow <jats:italic>in\u00a0vitro<\/jats:italic> in the absence of cytokines (Flt3\u2010ligand and interleukin\u20107), which did not occur with any two\u2010gene combination. Although transplanted T cells were a mixture of cells transduced with different combinations of the genes, tumors that developed in mice were composed of <jats:italic><jats:styled-content style=\"fixed-case\">HBZ<\/jats:styled-content><\/jats:italic>\/<jats:italic><jats:styled-content style=\"fixed-case\">BCL<\/jats:styled-content>xL<\/jats:italic>\/<jats:italic><jats:styled-content style=\"fixed-case\">AKT<\/jats:styled-content><\/jats:italic> triply transduced T cells, showing the synergistic effect of the three genes. The genetic\/epigenetic landscape of <jats:styled-content style=\"fixed-case\">ATL<\/jats:styled-content> has only recently been elucidated, and the roles of additional \u201chits\u201d in <jats:styled-content style=\"fixed-case\">ATL<\/jats:styled-content> pathogenesis remain to be explored. Our model provides a versatile tool to examine the roles of these hits, in collaboration with <jats:italic><jats:styled-content style=\"fixed-case\">HBZ<\/jats:styled-content><\/jats:italic>, in the development of acute <jats:styled-content style=\"fixed-case\">ATL<\/jats:styled-content>.<\/jats:p>","DOI":"10.1111\/cas.12974","type":"journal-article","created":{"date-parts":[[2016,5,25]],"date-time":"2016-05-25T23:20:42Z","timestamp":1464218442000},"page":"1072-1078","source":"Crossref","is-referenced-by-count":7,"title":["New mouse model of acute adult T\u2010cell leukemia generated by transplantation of <i>AKT<\/i>,<i> BCLxL<\/i>, and <i>HBZ<\/i>\u2010transduced T cells"],"prefix":"10.1111","volume":"107","author":[{"given":"Yumiko","family":"Kasugai","sequence":"first","affiliation":[{"name":"Division of Molecular Medicine Aichi Cancer Center Research Institute Nagoya Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7001-0106","authenticated-orcid":false,"given":"Noriaki","family":"Yoshida","sequence":"additional","affiliation":[{"name":"Department of Pathology Kurume University School of Medicine Kurume Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Koichi","family":"Ohshima","sequence":"additional","affiliation":[{"name":"Department of Pathology Kurume University School of Medicine Kurume Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1761-6314","authenticated-orcid":false,"given":"Keitaro","family":"Matsuo","sequence":"additional","affiliation":[{"name":"Division of Molecular Medicine Aichi Cancer Center Research Institute Nagoya Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masao","family":"Seto","sequence":"additional","affiliation":[{"name":"Department of Pathology Kurume University School 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