SEARCH:   Advanced

Blood, 28 May 2009, Vol. 113, No. 22, pp. 5599-5604. Prepublished online as a Blood First Edition Paper on February 27, 2009; DOI 10.1182/blood-2008-12-195255. This Article Full Text Full Text (PDF) All Versions of this Article: blood-2008-12-195255v1 113/22/5599    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 Hilton, D. J. Articles by Alexander, W. S. PubMed PubMed Citation Articles by Hilton, D. J. Articles by Alexander, W. S. Related Collections Platelets and Thrombopoiesis Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  PLATELETS AND THROMBOPOIESIS Mutational inhibition of c-Myb or p300 ameliorates treatment-induced thrombocytopenia Douglas J. Hilton1, Benjamin T. Kile1, and Warren S. Alexander2 1 Molecular Medicine Division and 2 Cancer and Haematology Division, Walter and Eliza Hall Institute of Medical Research, Parkville, Australia The transcription factor c-Myb and coregulator p300 have a key role in maintaining production of controlled numbers of megakaryocytes and platelets. In mice, mutations in c-Myb or p300 cause thrombocytosis in otherwise wild-type animals and can ameliorate the thrombocytopenia in mice lacking the thrombopoietin receptor, c-Mpl, a model for human congenital amegakaryocytic thrombocytopenia. To examine whether inhibition of c-Myb/p300 is effective in other models of thrombocytopenia, the effect of the c-MybPlt4 mutation on thrombocytopenia associated with reduced platelet life span in Bcl-XPlt20/Plt20 mice was assessed, as were responses in c-MybPlt4 and/or p300Plt6 mutant mice to thrombocytopenia associated with antiplatelet antibodies, chemotherapy, or bone marrow transplantation. Homozygosity of the c-MybPlt4 allele ameliorated thrombocytopenia associated with reduced platelet life span, and c-MybPlt4/+ mice exhibited more rapid than normal recovery from thrombocytopenia caused by antiplatelet serum or bone marrow transplantation. Recovery to pretreatment platelet levels was unaltered in 5-fluorouracil–treated c-MybPlt4/+ mice relative to wild-type controls, but enhanced platelet production during subsequent thrombocytosis was evident. More modest enhancement of platelet recovery after 5-fluorouracil or bone marrow transplantation was also evident in p300Plt6/+ animals. The data suggest potential utility of c-Myb/p300 as a target for therapeutic intervention in thrombocytopenia of diverse origins. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

	Copyright © 2009 by American Society of Hematology         Online ISSN: 1528-0020