SEARCH:   Advanced

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 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 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 HighWire Citing Articles via CrossRef Google Scholar Articles by Yu, J. Articles by Caligiuri, M. A. PubMed PubMed Citation Articles by Yu, J. Articles by Caligiuri, M. A. Related Collections Hematopoiesis and Stem Cells Immunobiology Lymphoid Neoplasia Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  LYMPHOID NEOPLASIA TSC-22 contributes to hematopoietic precursor cell proliferation and repopulation and is epigenetically silenced in large granular lymphocyte leukemia Jianhua Yu1,2, Maxim Ershler3, Li Yu4, Min Wei1,2, Björn Hackanson1,5, Akihiko Yokohama1,2, Takeki Mitsui1,2, Chunhui Liu1,2, Hsiaoyin Mao1,2, Shujun Liu1,2, Zhongfa Liu6, Rossana Trotta1,2, Chang-gong Liu1, Xiuping Liu1, Kun Huang7, Jan Visser8, Guido Marcucci1,2,9, Christoph Plass1,9, Alexander V. Belyavsky10, and Michael A. Caligiuri1,2,9 1 Department of Molecular Virology, Immunology, and Medical Genetics, and 2 Division of Hematology/Oncology, Department of Internal Medicine, The Ohio State University, Columbus; 3 Hematopoiesis Physiology Laboratory, Hematological Research Center, Russian Academy of Medical Sciences, Moscow, Russia; 4 Department of Hematology, 301 General Hospital of PLA, Beijing, People's Republic of China; 5 Department of Hematology and Oncology, University of Freiburg Medical Center, Freiburg, Germany; 6 College of Pharmacy, and 7 Department of Medical Informatics, The Ohio State University, Columbus; 8 ViaCell, Cambridge, MA; 9 The Ohio State University Comprehensive Cancer Center, James Cancer Hospital and Solove Research Institute, Columbus; and 10 Laboratory of Molecular Biology of Development, Engelhardt Institute of Molecular Biology RAS, Moscow, Russia 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 natural killer (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 (HPCs). Collectively, our data suggest that TSC-22 normally contributes to the regulation of HPC function and is a putative tumor suppressor gene that 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]

	Copyright © 2009 by American Society of Hematology         Online ISSN: 1528-0020