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Blood, 15 July 2005, Vol. 106, No. 2, pp. 494-504. Prepublished online as a Blood First Edition Paper on March 22, 2005; DOI 10.1182/blood-2004-08-3280. This Article Full Text (PDF) All Versions of this Article: 2004-08-3280v1 106/2/494    most recent Alert me when this article is cited Alert me if a correction is posted 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 Growney, J. D Articles by Gilliland, D G Search for Related Content PubMed PubMed Citation Articles by Growney, J. D Articles by Gilliland, D G Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted August 26, 2004 Accepted March 16, 2005 Loss of Runx1 perturbs adult hematopoiesis and is associated with a myeloproliferative phenotype Joseph D Growney, Hirokazu Shigematsu, Zhe Li, Benjamin H Lee, Jennifer Adelsperger, Rebecca Rowan, David P Curley, Jeffery L Kutok, Koichi Akashi, Ifor R Williams, Nancy A Speck, and D G Gilliland* Division of Hematology, Brigham and Women's Hospital, Boston, MA, USA Cancer Immunology and AIDS, Dana-Farber Cancer Institute, Boston, MA, USA Department of Biochemistry, Dartmouth Medical School, Hanover, NH, USA Division of Hematology, Brigham and Women's Hospital, Boston, MA, USA; Department of Pathology, Brigham and Women's Hospital, Boston, MA, USA Department of Pathology, Brigham and Women's Hospital, Boston, MA, USA Department of Pathology, Emory University, Atlanta, GA, USA Division of Hematology, Brigham and Women's Hospital, Boston, MA, USA; Howard Hughes Medical Institute, Harvard Medical School, Boston, MA, USA * Corresponding author; email: ggilliland{at}rics.bwh.harvard.edu. Homozygous loss of function of Runx1 during murine development results in an embryonic lethal phenotype characterized by a complete lack of definitive hematopoiesis. In light of recent reports of disparate requirements for hematopoietic transcription factors during development as opposed to adult hematopoiesis, we employed a conditional gene targeting strategy to effect loss of Runx1 function in adult mice. In contrast with the critical role of Runx1 during development, Runx1 was not essential for hematopoiesis in the adult hematopoietic compartment, although there were a number of significant hematopoietic abnormalities observed. Runx1 excision had lineage specific effects on B- and T-cell maturation, as well as pronounced inhibition of common lymphocyte progenitor production. Runx1 excision also resulted in inefficient platelet production. Of note, Runx1 deficient mice developed a mild myeloproliferative phenotype characterized by an increase in peripheral blood neutrophils, an increase in myeloid progenitor populations, and extramedullary hematopoiesis comprised of maturing myeloid and erythroid elements. These findings indicate that Runx1 deficiency has markedly different consequences during development compared with adult hematopoiesis, and provides insights into the phenotypic manifestations of Runx1 deficiency in hematopoietic malignancies. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: G. R.A. Ehrhardt, A. Hijikata, H. Kitamura, O. Ohara, J.-Y. Wang, and M. D. Cooper Discriminating gene expression profiles of memory B cell subpopulations J. Exp. Med., July 14, 2008; (2008) jem.20072682. [Abstract] [Full Text] [PDF] S. D. Nimer Myelodysplastic syndromes Blood, May 15, 2008; 111(10): 4841 - 4851. [Abstract] [Full Text] [PDF] F. 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