{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T16:45:05Z","timestamp":1791305105866,"version":"4.3.1"},"reference-count":42,"publisher":"National Academy of Sciences","issue":"25","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[1997,12,9]]},"abstract":"<jats:p>\n                    Human T cell leukemia\/lymphotropic virus type I (HTLV-I) induces adult T cell leukemia\/lymphoma (ATLL). The mechanism of HTLV-I oncogenesis in T cells remains partly elusive.\n                    <jats:italic>In vitro<\/jats:italic>\n                    , HTLV-I induces ligand-independent transformation of human CD4\n                    <jats:sup>+<\/jats:sup>\n                    T cells, an event that correlates with acquisition of constitutive phosphorylation of Janus kinases (JAK) and signal transducers and activators of transcription (STAT) proteins. However, it is unclear whether the\n                    <jats:italic>in vitro<\/jats:italic>\n                    model of HTLV-I transformation has relevance to viral leukemogenesis\n                    <jats:italic>in vivo<\/jats:italic>\n                    . Here we tested the status of JAK\/STAT phosphorylation and DNA-binding activity of STAT proteins in cell extracts of uncultured leukemic cells from 12 patients with ATLL by either DNA-binding assays, using DNA oligonucleotides specific for STAT-1 and STAT-3, STAT-5 and STAT-6 or, more directly, by immunoprecipitation and immunoblotting with anti-phosphotyrosine antibody for JAK and STAT proteins. Leukemic cells from 8 of 12 patients studied displayed constitutive DNA-binding activity of one or more STAT proteins, and the constitutive activation of the JAK\/STAT pathway was found to persist over time in the 2 patients followed longitudinally. Furthermore, an association between JAK3 and STAT-1, STAT-3, and STAT-5 activation and cell-cycle progression was demonstrated by both propidium iodide staining and bromodeoxyuridine incorporation in cells of four patients tested. These results imply that JAK\/STAT activation is associated with replication of leukemic cells and that therapeutic approaches aimed at JAK\/STAT inhibition may be considered to halt neoplastic growth.\n                  <\/jats:p>","DOI":"10.1073\/pnas.94.25.13897","type":"journal-article","created":{"date-parts":[[2002,7,26]],"date-time":"2002-07-26T10:31:39Z","timestamp":1027679499000},"page":"13897-13902","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":227,"title":["Proliferation of adult T cell leukemia\/lymphoma cells is associated with the constitutive activation of  JAK\/STAT\u2009proteins"],"prefix":"10.1073","volume":"94","author":[{"given":"Shigeki","family":"Takemoto","sequence":"first","affiliation":[{"name":"Basic Research Laboratory, Division of Basic Sciences, Laboratory of Cellular and Molecular Biology, and Metabolism Branch, Division of Clinical Sciences, National Cancer Institute, Bethesda, MD 20892; Laboratory of Molecular Immunology, National Heart, Lung, and Blood Institute, Bethesda, MD 20892; Second Department of Internal Medicine, Kumamoto University School of Medicine, Japan; and Department of Laboratory Medicine, Nagasaki University School of Medicine, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James C.","family":"Mulloy","sequence":"additional","affiliation":[{"name":"Basic Research Laboratory, Division of Basic Sciences, Laboratory of Cellular and Molecular Biology, and Metabolism Branch, Division of Clinical Sciences, National Cancer Institute, Bethesda, MD 20892; Laboratory of Molecular Immunology, National Heart, Lung, and Blood Institute, Bethesda, MD 20892; Second Department of Internal Medicine, Kumamoto University School of Medicine, Japan; and Department of Laboratory Medicine, Nagasaki University School of Medicine, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Cereseto","sequence":"additional","affiliation":[{"name":"Basic Research Laboratory, Division of Basic Sciences, Laboratory of Cellular and Molecular Biology, and Metabolism Branch, Division of Clinical Sciences, National Cancer Institute, Bethesda, MD 20892; Laboratory of Molecular Immunology, National Heart, Lung, and Blood Institute, Bethesda, MD 20892; Second Department of Internal Medicine, Kumamoto University School of Medicine, Japan; and Department of Laboratory Medicine, Nagasaki University School of Medicine, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thi-Sao","family":"Migone","sequence":"additional","affiliation":[{"name":"Basic Research Laboratory, Division of Basic Sciences, Laboratory of Cellular and Molecular Biology, and Metabolism Branch, Division of Clinical Sciences, National Cancer Institute, Bethesda, MD 20892; Laboratory of Molecular Immunology, National Heart, Lung, and Blood Institute, Bethesda, MD 20892; Second Department of Internal Medicine, Kumamoto University School of Medicine, Japan; and Department of Laboratory Medicine, Nagasaki University School of Medicine, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barvin K. R.","family":"Patel","sequence":"additional","affiliation":[{"name":"Basic Research Laboratory, Division of Basic Sciences, Laboratory of Cellular and Molecular Biology, and Metabolism Branch, Division of Clinical Sciences, National Cancer Institute, Bethesda, MD 20892; Laboratory of Molecular Immunology, National Heart, Lung, and Blood Institute, Bethesda, MD 20892; Second Department of Internal Medicine, Kumamoto University School of Medicine, Japan; and Department of Laboratory Medicine, Nagasaki University School of Medicine, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masao","family":"Matsuoka","sequence":"additional","affiliation":[{"name":"Basic Research Laboratory, Division of Basic Sciences, Laboratory of Cellular and Molecular Biology, and Metabolism Branch, Division of Clinical Sciences, National Cancer Institute, Bethesda, MD 20892; Laboratory of Molecular Immunology, National Heart, Lung, and Blood Institute, Bethesda, MD 20892; Second Department of Internal Medicine, Kumamoto University School of Medicine, Japan; and Department of Laboratory Medicine, Nagasaki University School of Medicine, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kuzunari","family":"Yamaguchi","sequence":"additional","affiliation":[{"name":"Basic Research Laboratory, Division of Basic Sciences, Laboratory of Cellular and Molecular Biology, and Metabolism Branch, Division of Clinical Sciences, National Cancer Institute, Bethesda, MD 20892; Laboratory of Molecular Immunology, National Heart, Lung, and Blood Institute, Bethesda, MD 20892; Second Department of Internal Medicine, Kumamoto University School of Medicine, Japan; and Department of Laboratory Medicine, Nagasaki University School of Medicine, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kiyoshi","family":"Takatsuki","sequence":"additional","affiliation":[{"name":"Basic Research Laboratory, Division of Basic Sciences, Laboratory of Cellular and Molecular Biology, and Metabolism Branch, Division of Clinical Sciences, National Cancer Institute, Bethesda, MD 20892; Laboratory of Molecular Immunology, National Heart, Lung, and Blood Institute, Bethesda, MD 20892; Second Department of Internal Medicine, Kumamoto University School of Medicine, Japan; and Department of Laboratory Medicine, Nagasaki University School of Medicine, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shimeru","family":"Kamihira","sequence":"additional","affiliation":[{"name":"Basic Research Laboratory, Division of Basic Sciences, Laboratory of Cellular and Molecular Biology, and Metabolism Branch, Division of Clinical Sciences, National Cancer Institute, Bethesda, MD 20892; Laboratory of Molecular Immunology, National Heart, Lung, and Blood Institute, Bethesda, MD 20892; Second Department of Internal Medicine, Kumamoto University School of Medicine, Japan; and Department of Laboratory Medicine, Nagasaki University School of Medicine, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeffrey D.","family":"White","sequence":"additional","affiliation":[{"name":"Basic Research Laboratory, Division of Basic Sciences, Laboratory of Cellular and Molecular Biology, and Metabolism Branch, Division of Clinical Sciences, National Cancer Institute, Bethesda, MD 20892; Laboratory of Molecular Immunology, National Heart, Lung, and Blood Institute, Bethesda, MD 20892; Second Department of Internal Medicine, Kumamoto University School of Medicine, Japan; and Department of Laboratory Medicine, Nagasaki University School of Medicine, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Warren J.","family":"Leonard","sequence":"additional","affiliation":[{"name":"Basic Research Laboratory, Division of Basic Sciences, Laboratory of Cellular and Molecular Biology, and Metabolism Branch, Division of Clinical Sciences, National Cancer Institute, Bethesda, MD 20892; Laboratory of Molecular Immunology, National Heart, Lung, and Blood Institute, Bethesda, MD 20892; Second Department of Internal Medicine, Kumamoto University School of Medicine, Japan; and Department of Laboratory Medicine, Nagasaki University School of Medicine, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Waldmann","sequence":"additional","affiliation":[{"name":"Basic Research Laboratory, Division of Basic Sciences, Laboratory of Cellular and Molecular Biology, and Metabolism Branch, Division of Clinical Sciences, National Cancer Institute, Bethesda, MD 20892; Laboratory of Molecular Immunology, National Heart, Lung, and Blood Institute, Bethesda, MD 20892; Second Department of Internal Medicine, Kumamoto University School of Medicine, Japan; and Department of Laboratory Medicine, Nagasaki University School of Medicine, 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