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Blood, 28 May 2009, Vol. 113, No. 22, pp. 5558-5567. Prepublished online as a Blood First Edition Paper on March 27, 2009; DOI 10.1182/blood-2009-02-205732. This Article Full Text (PDF) Supplemental Methods and Figures All Versions of this Article: blood-2009-02-205732v1 113/22/5558    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 HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Yu, J. Articles by Caligiuri, M. A. Search for Related Content PubMed PubMed Citation Articles by Yu, J. Articles by Caligiuri, M. A. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted February 17, 2009 Accepted March 8, 2009 TSC-22 contributes to hematopoietic precursor cell proliferation and repopulation and is epigenetically silenced in large granular lymphocyte leukemia Jianhua Yu*, Maxim Ershler, Li Yu, Min Wei, Bjorn Hackanson, Akihiko Yokohama, Takeki Mitsui, Chunhui Liu, Hsiaoyin Mao, Shujun Liu, Zhongfa Liu, Rossana Trotta, Chang-gong Liu, Xiuping Liu, Kun Huang, Jan Visser, Guido Marcucci, Christoph Plass, Alexander V. Belyavsky, and Michael A. Caligiuri Department of Molecular Virology, Immunology, and Medical Genetics, The Ohio State University, Columbus, OH, United States Hematopoiesis Physiology Lab, Hematological Research Center, Russian Academy of Medical Sciences, Moscow, Russian Federation Department of Hematology, 301 General Hospital of PLA, Beijing, China Division of Hematology/Oncology, Department of Internal Medicine, The Ohio State University, Columbus, OH, United States Department of Hematology and Oncology, University of Freiburg Medical Center, Freiburg, Germany College of Pharmacy, The Ohio State University, Columbus, OH, United States Department of Medical Bioinformatics, The Ohio State University, Columbus, OH, United States ViaCell Inc, Cambridge, MA, United States The Ohio State University Comprehensive Cancer Center, James Cancer Hospital and Solove Research Institute, Columbus, OH, United States Laboratory of Molecular Biology of Development, Engelhardt Institute of Molecular Biology RAS, Moscow, Russian Federation * Corresponding author; email: jianhua.yu{at}osumc.edu. Aberrant methylation of tumor suppressor genes can lead to their silencing in many cancers. TSC-22 is a gene silenced in several solid tumors, but its function and the mechanism(s) responsible for its silencing are largely unknown. Here we demonstrate that the TSC-22 promoter is methylated in primary mouse T or NK large granular lymphocyte (LGL) leukemia and this is associated with down regulation or silencing of TSC-22 expression. The TSC-22 deregulation was reversed in vivo by a 5-aza-2'-deoxycytidine therapy of T or NK LGL leukemia, which significantly increased survival of the mice bearing this disease. Ectopic expression of TSC-22 in mouse leukemia or lymphoma cell lines resulted in delayed in vivo tumor formation. Targeted disruption of TSC-22 in wild type mice enhanced proliferation and in vivo repopulation efficiency of hematopoietic precursor cells (HPC). Collectively, our data suggest that TSC-22 normally contributes to the regulation of HPC function and is a putative tumor suppressor gene which is hypermethylated and silenced in T or NK LGL leukemia. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: R. Zambello and G. Semenzato Large granular lymphocyte disorders: new etiopathogenetic clues as a rationale for innovative therapeutic approaches Haematologica, October 1, 2009; 94(10): 1341 - 1345. [Full Text] [PDF]

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