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Blood, 3 September 2009, Vol. 114, No. 10, pp. 2087-2096. Prepublished online as a Blood First Edition Paper on June 19, 2009; DOI 10.1182/blood-2009-01-197921. This Article Full Text Full Text (PDF) Supplemental Tables and Figures All Versions of this Article: blood-2009-01-197921v1 114/10/2087    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 Google Scholar Articles by Niu, C. Articles by Morris, S. W. PubMed PubMed Citation Articles by Niu, C. Articles by Morris, S. W. Related Collections Hematopoiesis and Stem Cells Platelets and Thrombopoiesis Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  HEMATOPOIESIS AND STEM CELLS c-Myc is a target of RNA-binding motif protein 15 in the regulation of adult hematopoietic stem cell and megakaryocyte development Chao Niu1, Jiwang Zhang2,3, Peter Breslin2,4, Mihaela Onciu1, Zhigui Ma5, and Stephan Wade Morris1,6 1 Department of Pathology, St Jude Children's Research Hospital, Memphis, TN; 2 Oncology Institute, Cardinal Bernardin Cancer Center, and 3 Pathology Department, Loyola University Medical Center, Maywood, IL; 4 Department of Biology, Loyola University, Chicago, IL; 5 Laboratory of Hematology, Department of Pediatric Hematology, West China Second University Hospital, Sichuan University, Chengdu, China; and 6 Department of Oncology, St Jude Children's Research Hospital, Memphis, TN RNA-binding motif protein 15 (RBM15) is involved in the RBM15-megakaryoblastic leukemia 1 fusion in acute megakaryoblastic leukemia. Although Rbm15 has been reported to be required for B-cell differentiation and to inhibit myeloid and megakaryocytic expansion, it is not clear what the normal functions of Rbm15 are in the regulation of hematopoietic stem cell (HSC) and megakaryocyte development. In this study, we report that Rbm15 may function in part through regulation of expression of the proto-oncogene c-Myc. Similar to c-Myc knockout (c-Myc-KO) mice, long-term (LT) HSCs are significantly increased in Rbm15-KO mice due to an apparent LT-HSC to short-term HSC differentiation defect associated with abnormal HSC-niche interactions caused by increased N-cadherin and β1 integrin expression on mutant HSCs. Both serial transplantation and competitive reconstitution capabilities of Rbm15-KO LT-HSCs are greatly compromised. Rbm15-KO and c-Myc-KO mice also share related abnormalities in megakaryocyte development, with mutant progenitors producing increased, abnormally small low-ploidy megakaryocytes. Consistent with a possible functional interplay between Rbm15 and c-Myc, the megakaryocyte increase in Rbm15-KO mice could be partially reversed by ectopic c-Myc. Thus, Rbm15 appears to be required for normal HSC-niche interactions, for the ability of HSCs to contribute normally to adult hematopoiesis, and for normal megakaryocyte development; these effects of Rbm15 on hematopoiesis may be mediated at least in part by c-Myc. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

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