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Blood, 3 September 2009, Vol. 114, No. 10, pp. 2097-2106. Prepublished online as a Blood First Edition Paper on April 16, 2009; DOI 10.1182/blood-2009-01-197947. This Article Full Text Full Text (PDF) Supplemental Appendix, Tables, and Figures All Versions of this Article: blood-2009-01-197947v1 114/10/2097    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 Guo, Y. Articles by Zhang, J. PubMed PubMed Citation Articles by Guo, Y. Articles by Zhang, J. Related Collections Hematopoiesis and Stem Cells Platelets and Thrombopoiesis Red Cells, Iron, and Erythropoiesis Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  HEMATOPOIESIS AND STEM CELLS c-Myc–mediated control of cell fate in megakaryocyte-erythrocyte progenitors Yinshi Guo1,*, Chao Niu2,*, Peter Breslin1,3, Minghui Tang1, Shubin Zhang1, Wei Wei1, Ameet R. Kini4, Gladell P. Paner4, Serhan Alkan4, Stephan W. Morris2, Manuel Diaz1, Patrick J. Stiff1, and Jiwang Zhang1,4 1 Oncology Institute, Cardinal Bernardin Cancer Center, Loyola University Medical Center, Maywood, IL; 2 Department of Pathology, St Jude Children's Research Hospital, Memphis, TN; 3 Department of Biology, Loyola University Chicago, IL; and 4 Pathology Department, Loyola University Medical Center, Maywood, IL It has been found that c-Myc protein plays a critical role in controlling self-renewal versus differentiation in hematopoietic stem cells. We report that c-Myc also controls the fate of megakaryocyte-erythrocyte progenitors through regulating the differentiation of erythroid and megakaryocytic progenitors. In addition to the significant reduction of granulocytes/macrophages and B and T lymphocytes because of the reduction of their corresponding progenitors, we found significantly increased numbers of megakaryocytic progenitors and mature megakaryocytes in bone marrow and spleens of c-Myc-knockout (c-Myc–/–) mice. Differentiation of erythrocytes was blocked at the erythroid progenitor stage. This increased megakaryocytopoiesis is a cell-intrinsic defect of c-Myc-mutant hematopoietic stem cells, as shown by transplantation studies. Furthermore, we found that c-Myc is required for polyploidy formation but not for cytoplasmic maturation of megakaryocytes. Megakaryocytes from c-Myc–/– mice are significantly smaller in size and lower in ploidy than those of control mice; however, because of the dramatic increase in megakaryocyte number, although fewer platelets are produced by each megakaryocyte, a greater than 3-fold increase in platelet number was consistently observed in c-Myc–/– mice. Thus, c-Myc–/– mice develop a syndrome of severe thrombocytosis-anemia-leukopenia because of significant increases in megakaryocytopoiesis and concomitant blockage of erythrocyte differentiation and reductions in myelolymphopoiesis. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: C. Niu, J. Zhang, P. Breslin, M. Onciu, Z. Ma, and S. W. Morris c-Myc is a target of RNA-binding motif protein 15 in the regulation of adult hematopoietic stem cell and megakaryocyte development Blood, September 3, 2009; 114(10): 2087 - 2096. [Abstract] [Full Text] [PDF]

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