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Blood, 1 May 2005, Vol. 105, No. 9, pp. 3480-3487. Prepublished online as a Blood First Edition Paper on January 21, 2005; DOI 10.1182/blood-2004-12-4806. This Article Full Text Full Text (PDF) All Versions of this Article: 2004-12-4806v1 105/9/3480    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 Citing Articles via Google Scholar Google Scholar Articles by Metcalf, D. Articles by Alexander, W. S. Search for Related Content PubMed PubMed Citation Articles by Metcalf, D. Articles by Alexander, W. S. Related Collections Hematopoiesis and Stem Cells Hemostasis, Thrombosis, and Vascular Biology Oncogenes and Tumor Suppressors Free Research Articles Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  HEMATOPOIESIS Anomalous megakaryocytopoiesis in mice with mutations in the c-Myb gene Donald Metcalf, Marina R. Carpinelli, Craig Hyland, Sandra Mifsud, Ladina DiRago, Nicos A. Nicola, Douglas J. Hilton, and Warren S. Alexander From the Division of Cancer and Hematology, The Walter and Eliza Hall Institute of Medical Research, Parkville, Australia. Mpl-/- mice bearing the Plt3 or Plt4 mutations in the c-Myb gene exhibit thrombopoietin (TPO)–independent supraphysiological platelet production accompanied by excessive megakaryocytopoiesis and defective erythroid and lymphoid cell production. To better define the cellular basis for the thrombocytosis in these mice, we analyzed the production and characteristics of megakaryocytes and their progenitors. Consistent with thrombocytosis arising from hyperactive production, the high platelet counts in mice carrying the c-MybPlt4 allele were not accompanied by any significant alteration in platelet half-life. Megakaryocytes in c-Myb mutant mice displayed reduced modal DNA ploidy and, among the excessive numbers of megakaryocyte progenitor cells, more mature precursors were particularly evident. Megakaryocyte progenitor cells carrying the Plt3 or Plt4 c-Myb mutations, but not granulocyte-macrophage progenitors, exhibited 200-fold enhanced responsiveness to granulocyte-macrophage colony-stimulating factor (GM-CSF), suggesting that altered responses to cytokines may contribute to expanded megakaryocytopoiesis. Mutant preprogenitor (blast colony-forming) cells appeared to have little capacity to form megakaryocyte progenitor cells. In contrast, the spleens of irradiated mice 12 days after transplantation with mutant bone marrow contained abundant megakaryocyte progenitor cells, suggesting that altered c-Myb activity skews differentiation commitment in spleen colony-forming units (CFU-S) in favor of excess megakaryocytopoiesis. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: Catastrophic for contaminated chickens, murder on mutant mice: harmful to human hematopoiesis? David P. Steensma Blood 2005 105: 3389-3390. [Full Text] [PDF] This article has been cited by other articles: T. I. Fortoul, A. Gonzalez-Villalva, G. Pinon-Zarate, V. Rodriguez-Lara, L. F. Montano, and L. Saldivar-Osorio Ultrastructural megakaryocyte modifications after vanadium inhalation in spleen and bone marrow J. Electron Microsc. (Tokyo), June 30, 2009; (2009) dfp031v1. [Abstract] [Full Text] [PDF] D. J. Hilton, B. T. Kile, and W. S. Alexander Mutational inhibition of c-Myb or p300 ameliorates treatment-induced thrombocytopenia Blood, May 28, 2009; 113(22): 5599 - 5604. [Abstract] [Full Text] [PDF] H. Zhao, A. Kalota, S. Jin, and A. M. Gewirtz The c-myb proto-oncogene and microRNA-15a comprise an active autoregulatory feedback loop in human hematopoietic cells Blood, January 15, 2009; 113(3): 505 - 516. [Abstract] [Full Text] [PDF] M. Kauppi, J. M. Murphy, C. A. de Graaf, C. D. Hyland, K. T. Greig, D. Metcalf, A. A. Hilton, N. A. Nicola, B. T. Kile, D. J. Hilton, et al. Point mutation in the gene encoding p300 suppresses thrombocytopenia in Mpl-/- mice Blood, October 15, 2008; 112(8): 3148 - 3153. [Abstract] [Full Text] [PDF] F. Bouilloux, G. Juban, N. Cohet, D. Buet, B. Guyot, W. Vainchenker, F. Louache, and F. Morle EKLF restricts megakaryocytic differentiation at the benefit of erythrocytic differentiation Blood, August 1, 2008; 112(3): 576 - 584. [Abstract] [Full Text] [PDF] Y. Nakata, S. Shetzline, C. Sakashita, A. Kalota, R. Rallapalli, S. I. Rudnick, Y. Zhang, S. G. Emerson, and A. M. Gewirtz c-Myb Contributes to G2/M Cell Cycle Transition in Human Hematopoietic Cells by Direct Regulation of Cyclin B1 Expression Mol. Cell. Biol., March 15, 2007; 27(6): 2048 - 2058. [Abstract] [Full Text] [PDF] E. Ferretti, J. C. Villaescusa, P. Di Rosa, L. C. Fernandez-Diaz, E. Longobardi, R. Mazzieri, A. Miccio, N. Micali, L. Selleri, G. Ferrari, et al. Hypomorphic Mutation of the TALE Gene Prep1 (pKnox1) Causes a Major Reduction of Pbx and Meis Proteins and a Pleiotropic Embryonic Phenotype Mol. Cell. Biol., August 1, 2006; 26(15): 5650 - 5662. [Abstract] [Full Text] [PDF] D. P. Steensma, A. Pardanani, W. S. Stevenson, R. Hoyt, H. Kiu, A. P. Grigg, J. Szer, S. Juneja, D. J. Hilton, W. S. Alexander, et al. More on Myb in myelofibrosis: molecular analyses of MYB and EP300 in 55 patients with myeloproliferative disorders Blood, February 15, 2006; 107(4): 1733 - 1735. [Full Text] [PDF]

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