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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 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 Citation Map 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 Citing Articles via Google Scholar Google Scholar Articles by Hidaka, T. Articles by Morishita, K. Search for Related Content PubMed PubMed Citation Articles by Hidaka, T. Articles by Morishita, K. Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  NEOPLASIA Down-regulation of TCF8 is involved in the leukemogenesis of adult T-cell leukemia/lymphoma Tomonori Hidaka1,2,*, Shingo Nakahata1,*, Kinta Hatakeyama3,*, Makoto Hamasaki1,4, Kiyoshi Yamashita2, Takashi Kohno5, Yasuhito Arai6, Tomohiko Taki7, Kazuhiro Nishida7, Akihiko Okayama8, Yujiro Asada3, Ryoji Yamaguchi9, Hirohito Tsubouchi2,10, Jun Yokota5, Masafumi Taniwaki7, Yujiro Higashi11, and Kazuhiro Morishita1 1 Division of Tumor and Cellular Biochemistry, Department of Medical Sciences, 2 Department of Internal Medicine II, University of Miyazaki, Miyazaki; 3 First Department of Pathology, Faculty of Medicine, University of Miyazaki, Miyazaki; 4 Miyazaki Prefectural Industrial Foundation, Miyazaki; 5 Biology Division, National Cancer Center Research Institute, Tokyo; 6 Cancer Genome Project, National Cancer Center Research Institute, Tokyo; 7 Department of Hematology and Oncology, Kyoto Prefectural University of Medicine, Kyoto; 8 Department of Rheumatology, Infectious Diseases and Laboratory Medicine, University of Miyazaki, Miyazaki; 9 Department of Veterinary Pathology, University of Miyazaki, Miyazaki; 10 Department of Digestive and Life-style related Disease, Kagoshima University Graduate School of Medicine and Dental Sciences, Kagoshima; and 11 Graduate School of Frontier Biosciences, Osaka University, Osaka, Japan 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, including mainly 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 β1 (TGF-β1), a well-known characteristic of ATLL cells, suggesting that escape from TGF-β1–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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