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Blood, 19 February 2009, Vol. 113, No. 8, pp. 1661-1669. Prepublished online as a Blood First Edition Paper on October 31, 2008; DOI 10.1182/blood-2008-01-135012. This Article Full Text (PDF) Supplemental Figures All Versions of this Article: blood-2008-01-135012v1 113/8/1661    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 Maillard, I. Articles by Hua, X. Search for Related Content PubMed PubMed Citation Articles by Maillard, I. Articles by Hua, X. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted January 23, 2008 Accepted October 18, 2008 Menin regulates the function of hematopoietic stem cells and lymphoid progenitors Ivan Maillard*, Ya-Xiong Chen, Ann Friedman, Yuqing Yang, Anthony T Tubbs, Olga Shestova, Warren S Pear, and Xianxin Hua Center for Stem Cell Biology, Life Sciences Institute, University of Michigan, Ann Arbor, MI, United States Abramson Family Cancer Research Institute, University of Pennsylvania, Philadelphia, PA, United States Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, PA, United States Institute of Medicine and Engineering, University of Pennsylvania, Philadelphia, PA, United States Department of Cancer Biology, University of Pennsylvania, Philadelphia, PA, United States * Corresponding author; email: imaillar{at}umich.edu. Men1 is a tumor suppressor gene mutated in endocrine neoplasms. Besides its endocrine role, the Men1 gene product menin interacts with the Mixed Lineage Leukemia (MLL) protein, a histone H3 lysine 4 methyltransferase. Although menin and MLL fusion proteins cooperate to activate Homeobox (Hox) gene expression during transformation, little is known about the normal hematopoietic functions of menin. Here we studied hematopoiesis after Men1 ablation. Menin loss modestly impaired blood neutrophil, lymphocyte and platelet counts. Without hematopoietic stress, multilineage and myelo-erythroid bone marrow progenitor numbers were preserved, while B lymphoid progenitors were decreased. In contrast, competitive transplantation revealed a marked functional defect of long-term hematopoietic stem cells (HSC) in the absence of menin, despite normal initial homing of progenitors to the bone marrow. HoxA9 gene expression was only modestly decreased in menin-deficient HSCs. These observations reveal a novel and essential role for menin in HSC homeostasis that was most apparent during situations of hematopoietic recovery, suggesting that menin regulates molecular pathways that are essential during the adaptive HSC response to stress. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: Y.-L. Hu, S. Fong, C. Ferrell, C. Largman, and W.-F. Shen HOXA9 Modulates Its Oncogenic Partner Meis1 To Influence Normal Hematopoiesis Mol. Cell. Biol., September 15, 2009; 29(18): 5181 - 5192. [Abstract] [Full Text] [PDF]

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