Anomalous megakaryocytopoiesis in mice with mutations in the c-Myb gene
Details
Publication Year 2005-05-01, Volume 105, Issue #9, Page 3480-3487
Journal Title
BLOOD
Publication Type
Journal Article
Abstract
Mpl(-/-) mice bearing the Plt3or 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-Myb(Plt4) 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 megakaryocytopolesis. 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 megakaryocytopolesis. (c) 2005 by The American Society of Hematology.
Publisher
AMER SOC HEMATOLOGY
Keywords
MPL-DEFICIENT MICE; HEMATOPOIETIC PROGENITORS; TRANSCRIPTION-FACTOR; MYELOID PROGENITORS; CELLS; THROMBOPOIETIN; DIFFERENTIATION; MULTIPOTENT; PLATELETS; BINDING
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Creation Date: 2005-05-01 12:00:00
Last Modified: 0001-01-01 12:00:00
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