NDLI: TSC-22 contributes to hematopoietic precursor cell proliferation and repopulation and is epigenetically silenced in large granular lymphocyte leukemia

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TSC-22 contributes to hematopoietic precursor cell proliferation and repopulation and is epigenetically silenced in large granular lymphocyte leukemia

Content Provider	Scilit
Author	Yu, Jianhua Ershler, Maxim Yu, Li Wei, Min Hackanson, Björn Yokohama, Akihiko Mitsui, Takeki Liu, Chunhui Mao, Hsiaoyin Liu, Shujun Liu, Zhongfa Trotta, Rossana Liu, Chang-Gong Liu, Xiuping Huang, Kun Visser, Jan Marcucci, Guido Plass, Christoph Belyavsky, Alexander V. Caligiuri, Michael A.
Copyright Year	2009
Description	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.
Related Links	http://www.bloodjournal.org/content/113/22/5558.full.pdf
Ending Page	5567
Page Count	10
Starting Page	5558
DOI	10.1182/blood-2009-02-205732
Journal	Blood
Issue Number	22
Volume Number	113
Language	English
Publisher	American Society of Hematology
Publisher Date	2009-05-28
Access Restriction	Open
Subject Keyword	Research and Experimental Medicine Hematopoietic Function Epigenetically Silenced Proliferation Repopulation Tsc Leukemia Hpcs Precursor Journal: Blood (Vol- 135, Issue- 22)
Content Type	Text
Resource Type	Article

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