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Blood, 15 April 2007, Vol. 109, No. 8, pp. 3432-3440. Prepublished online as a Blood First Edition Paper on December 21, 2006; DOI 10.1182/blood-2006-10-051508. This Article Full Text (PDF) Supplemental Figure All Versions of this Article: blood-2006-10-051508v1 109/8/3432    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 Zhao, L. Articles by Liu, P P. Search for Related Content PubMed PubMed Citation Articles by Zhao, L. Articles by Liu, P P. Related Collections Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted October 10, 2006 Accepted December 4, 2006 CBFB-MYH11 hinders early T cell development and induces massive cell death in the thymus Ling Zhao, Jennifer L Cannons, Stacie Anderson, Martha Kirby, Liping Xu, Lucio H Castilla, Pamela L. Schwartzberg, Remy Bosselut, and P Paul Liu* Genetics and Molecular Biology Branch, NHGRI, NIH, Bethesda, MD, United States Genetic Disease Research Branch, NHGRI, NIH, Bethesda, MD, United States Program in Gene Function and Expression, University of Massachusetts Medical School, Worcester, MA, United States Laboratory of Immune Cell Biology, Center for Cancer Researc, NCI, NIH, Bethesda, MD, United States * Corresponding author; email: pliu{at}nhgri.nih.gov. Recent studies suggest that the chromosome 16 inversion, associated with acute myeloid leukemia M4Eo, takes place in hematopoietic stem cells. If this is the case, it is of interest to know the effects of the resulting fusion gene, CBFB-MYH11, on other lineages. Here we studied T cell development in mice expressing Cbfb-MYH11 and compared them with mice compound-heterozygous for a Cbfb null and a hypomorphic GFP knock-in allele (Cbfb-/GFP), which had severe Cbfb deficiency. We found a differentiation block at the DN1 stage of thymocyte development in Cbfb-MYH11 knock-in chimeras. In a conditional knock-in model in which Cbfb-MYH11 expression was activated by Lck-Cre, there was a 10-fold reduction in thymocyte numbers in adult thymus, resulting mainly from impaired survival of CD4+CD8+ thymocytes. Although Cbfb-MYH11 derepressed CD4 expression efficiently in reporter assays, such derepression was less pronounced in vivo. On the other hand, CD4 expression was derepressed and thymocyte development was blocked at DN1 and DN2 stages in E17.5 Cbfb-/GFP thymus, with a 20-fold reduction of total thymocyte numbers. Our data suggest that Cbfb-MYH11 suppressed Cbfb in several stages of T cell development and provide a mechanism for CBFB-MYH11 association with myeloid but not lymphoid leukemia. 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]

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