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Blood, 15 February 2008, Vol. 111, No. 4, pp. 1894-1902. Prepublished online as a Blood First Edition Paper on November 29, 2007; DOI 10.1182/blood-2007-02-071746. This Article Full Text Full Text (PDF) Supplemental Figures All Versions of this Article: blood-2007-02-071746v1 111/4/1894    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 Citing Articles via Google Scholar Google Scholar Articles by Daria, D. Articles by Geiger, H. Search for Related Content PubMed PubMed Citation Articles by Daria, D. Articles by Geiger, H. Related Collections Hematopoiesis and Stem Cells Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  HEMATOPOIESIS The retinoblastoma tumor suppressor is a critical intrinsic regulator for hematopoietic stem and progenitor cells under stress Deidre Daria1, Marie-Dominique Filippi1, Erik S. Knudsen2, Roberta Faccio3, Zhixiong Li4, Theodosia Kalfa1,5, and Hartmut Geiger1 1 Division of Experimental Hematology, Cincinnati Children's Hospital Medical Center, Department of Medicine, University of Cincinnati, OH; 2 Department of Cell Biology, Vontz Center for Molecular Studies, University of Cincinnati, OH; 3 Department of Orthopedic Surgery, Washington University School of Medicine, St Louis, MO; 4 Department of Experimental Hematology, Hanover Medical School, Hanover, Germany; and 5 Division of Hematology/Oncology, Cincinnati Children's Hospital Medical Center, Department of Medicine, University of Cincinnati, OH The retinoblastoma tumor suppressor protein (RB) plays important roles in the control of the cell division cycle. It is estimated that RB is dysfunctional/inactivated in up to 40% of human leukemias. The consequences of loss of RB on hematopoietic stem and progenitor cell (HSPC) function in vivo are incompletely understood. Here, we report that mice genetically deficient in Rb in all hematopoietic cells (Vav-Cre Rb knockout [KO] animals) showed altered contribution of distinct hematopoietic cell lineages to peripheral blood, bone marrow, and spleen; significantly increased extramedullary hematopoiesis in the spleen; and a 2-fold increase in the frequency of hematopoietic progenitor cells in peripheral blood. Upon competitive transplantation, HSPCs from Vav-Cre Rb KO mice contributed with an at least 4- to 6-fold less efficiency to hematopoiesis compared with control cells. HSPCs deficient in Rb presented with impaired cell-cycle exit upon stress-induced proliferation, which correlated with impaired function. In summary, Rb is critical for hematopoietic stem and progenitor cell function, localization, and differentiation. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

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