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Blood, 1 January 2007, Vol. 109, No. 1, pp. 11-21. Prepublished online as a Blood First Edition Paper on August 29, 2006; DOI 10.1182/blood-2006-05-021188. This Article Full Text Full Text (PDF) All Versions of this Article: blood-2006-05-021188v1 109/1/11    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 Talebian, L. Articles by Speck, N. A. Search for Related Content PubMed PubMed Citation Articles by Talebian, L. Articles by Speck, N. A. Related Collections Hematopoiesis and Stem Cells Hemostasis, Thrombosis, and Vascular Biology Immunobiology Plenary Papers Gene Expression Free Research Articles Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  PLENARY PAPER T-lymphoid, megakaryocyte, and granulocyte development are sensitive to decreases in CBFß dosage. Laleh Talebian1, Zhe Li1, Yalin Guo1, Justin Gaudet1, Maren E. Speck1, Daisuke Sugiyama1, Prabhjot Kaur2, Warren S. Pear3, Ivan Maillard4,, and Nancy A. Speck1, 1 Department of Biochemistry, Dartmouth Medical School, Hanover, NH; 2 Department of Pathology, Dartmouth Medical School, Hanover, NH; 3 Department of Pathology & Laboratory Medicine, Abramson Family Cancer Research Institute, Institute for Medicine & Engineering, University of Pennsylvania, Philadelphia, PA; and 4 Division of Hematology-Oncology, University of Pennsylvania School of Medicine, Philadelphia, PA The family of core-binding factors includes the DNA-binding subunits Runx1-3 and their common non–DNA-binding partner CBFß. We examined the collective role of core-binding factors in hematopoiesis with a hypomorphic Cbfb allelic series. Reducing CBFß levels by 3- or 6-fold caused abnormalities in bone development, megakaryocytes, granulocytes, and T cells. T-cell development was very sensitive to an incremental reduction of CBFß levels: mature thymocytes were decreased in number upon a 3-fold reduction in CBFß levels, and were virtually absent when CBFß levels were 6-fold lower. Partially penetrant consecutive differentiation blocks were found among early T-lineage progenitors within the CD4–CD8– double-negative 1 and downstream double-negative 2 thymocyte subsets. Our data define a critical CBFß threshold for normal T-cell development, and situate an essential role for core-binding factors during the earliest stages of T-cell development. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: The CBFB-MYH11 butterfly effect in hematopoiesis Andre J. van Wijnen and Gary S. Stein Blood 2007 109: 3131-3132. [Full Text] [PDF] This article has been cited by other articles: K. F. Wildt, G. Sun, B. Grueter, M. Fischer, M. Zamisch, M. Ehlers, and R. Bosselut The Transcription Factor Zbtb7b Promotes CD4 Expression by Antagonizing Runx-Mediated Activation of the CD4 Silencer J. Immunol., October 1, 2007; 179(7): 4405 - 4414. [Abstract] [Full Text] [PDF] A. J. van Wijnen and G. S. Stein The CBFB-MYH11 butterfly effect in hematopoiesis Blood, April 15, 2007; 109(8): 3131 - 3132. [Full Text] [PDF] L. Zhao, J. L. Cannons, S. Anderson, M. Kirby, L. Xu, L. H. Castilla, P. L. Schwartzberg, R. Bosselut, and P. P. Liu CBFB-MYH11 hinders early T-cell development and induces massive cell death in the thymus Blood, April 15, 2007; 109(8): 3432 - 3440. [Abstract] [Full Text] [PDF]

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