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Blood, 15 July 2008, Vol. 112, No. 2, pp. 383-393. Prepublished online as a Blood First Edition Paper on May 8, 2008; DOI 10.1182/blood-2008-01-131185. This Article Full Text (PDF) Supplemental Methods and Tables Supplemental Tables and Supplemental Figures All Versions of this Article: blood-2008-01-131185v1 112/2/383    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via CrossRef Google Scholar Articles by Hidaka, T. Articles by Morishita, K. PubMed PubMed Citation Articles by Hidaka, T. Articles by Morishita, K. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted January 7, 2008 Accepted April 4, 2008 Down-regulation of TCF8 is involved in the leukemogenesis of adult-T cell leukemia/lymphoma Tomonori Hidaka, Shingo Nakahata, Kinta Hatakeyama, Makoto Hamasaki, Kiyoshi Yamashita, Takashi Kohno, Yasuhito Arai, Tomohiko Taki, Kazuhiro Nishida, Akihiko Okayama, Yujiro Asada, Ryoji Yamaguchi, Hirohito Tsubouchi, Jun Yokota, Masafumi Taniwaki, Yujiro Higashi, and Kazuhiro Morishita* Division of Tumor and Cellular Biochemistry, Department of Medical Sciences, Faculty of Medicine, University of Miyazaki, Miyazaki, Japan First Department of Pathology, Faculty of Medicine, University of Miyazaki, Miyazaki, Japan Miyazaki Prefectural Industrial Foundation, Faculty of Medicine, University of Miyazaki, Miyazaki, Japan Department of Internal Medicine II, Faculty of Medicine, University of Miyazaki, Miyazaki, Japan Biology Division, National Cancer Center Research Institute, Tokyo, Japan Cancer Genome Project, National Cancer Center Research Institute, Tokyo, Japan Department of Hematology and Oncology, Kyoto Prefectural University of Medicine, Kyoto, Japan Department of Rheumatology, Infectious Diseases and Laboratory Medicine, Faculty of Medicine, University of Miyazaki, Miyazaki, Japan Department of Veterinary Pathology, University of Miyazaki, Miyazaki, Japan Department of Digestive and Live-style related Disease, Kagoshima University Graduate School of Medicine and Dental Sciences, Kagoshima, Japan Graduate School of Frontier Biosciences, Osaka University, Osaka, Japan * Corresponding author; email: kmorishi{at}med.miyazaki-u.ac.jp. Adult T-cell leukemia/lymphoma (ATLL) is caused by latent human T-lymphotropic virus-1 (HTLV-1) infection. To clarify the molecular mechanism underlying leukemogenesis after viral infection, we precisely mapped 605 chromosomal breakpoints in 61 ATLL cases by spectral karyotyping and identified frequent chromosomal breakpoints in 10p11, 14q11, and 14q32. Single nucleotide polymorphism (SNP) array-comparative genomic hybridization (CGH), genetic, and expression analyses of the genes mapped within a common breakpoint cluster region in 10p11.2 revealed that in ATLL cells, transcription factor 8 (TCF8) was frequently disrupted by several mechanisms, mainly including epigenetic dysregulation. TCF8-mutant mice frequently developed invasive CD4+ T-cell lymphomas in the thymus or in ascitic fluid in vivo. Down-regulation of TCF8 expression in ATLL cells in vitro was associated with resistance to transforming growth factor (TGF)-1, a well-known characteristic of ATLL cells, suggesting that escape from TGF-1-mediated growth inhibition is important in the pathogenesis of ATLL. These findings indicate that TCF8 has a tumor suppressor role in ATLL. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

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