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This Article Full Text Full Text (PDF) 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 Miller, J. D. Articles by Speck, N. A. Search for Related Content PubMed PubMed Citation Articles by Miller, J. D. Articles by Speck, N. A. Related Collections Hematopoiesis and Stem Cells Neoplasia Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  Blood, 15 April 2001, Vol. 97, No. 8, pp. 2248-2256 HEMATOPOIESIS Core-binding factor  (CBF), but not CBF-smooth muscle myosin heavy chain, rescues definitive hematopoiesis in CBF-deficient embryonic stem cells Janelle D. Miller, Terryl Stacy, P. Paul Liu, and Nancy A. Speck From the Department of Biochemistry, Dartmouth Medical School, Hanover, NH; and the Oncogenesis and Development Section, Genetics and Molecular Biology Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD. Core-binding factor  (CBF) is the non-DNA-binding subunit of the heterodimeric CBFs. Genes encoding CBF (CBFB), and one of the DNA-binding CBF subunits, Runx1 (also known as CBF2, AML1, and PEBP2B), are required for normal hematopoiesis and are also frequent targets of chromosomal translocations in acute leukemias in humans. Homozygous disruption of either the Runx1 or Cbfb gene in mice results in embryonic lethality at midgestation due to hemorrhaging in the central nervous system, and severely impairs fetal liver hematopoiesis. Results of this study show that Cbfb-deficient mouse embryonic stem (ES) cells can differentiate into primitive erythroid colonies in vitro, but are impaired in their ability to produce definitive erythroid and myeloid colonies, mimicking the in vivo defect. Definitive hematopoiesis is restored by ectopic expression of full-length Cbfb transgenes, as well as by a transgene encoding only the heterodimerization domain of CBF. In contrast, the CBF-smooth muscle myosin heavy chain (SMMHC) fusion protein generated by the inv(16) associated with acute myeloid leukemias (M4Eo) cannot rescue definitive hematopoiesis by Cbfb-deficient ES cells. Sequences responsible for the inability of CBF-SMMHC to rescue definitive hematopoiesis reside in the SMMHC portion of the fusion protein. Results also show that the CBF-SMMHC fusion protein transdominantly inhibits definitive hematopoiesis, but not to the same extent as homozygous loss of Runx1 or Cbfb. CBF-SMMHC preferentially inhibits the differentiation of myeloid lineage cells, while increasing the number of blastlike cells in culture. © 2001 by The American Society of Hematology.   CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: D. Li, K. K. Sinha, M. A. Hay, C. R. Rinaldi, Y. Saunthararajah, and G. Nucifora RUNX1-RUNX1 Homodimerization Modulates RUNX1 Activity and Function J. Biol. Chem., May 4, 2007; 282(18): 13542 - 13551. [Abstract] [Full Text] [PDF] S. A. Heilman, Y.-H. Kuo, C. S. Goudswaard, P. J. Valk, and L. H. Castilla Cbf{beta} Reduces Cbf{beta}-SMMHC-Associated Acute Myeloid Leukemia in Mice Cancer Res., December 1, 2006; 66(23): 11214 - 11218. [Abstract] [Full Text] [PDF] G. Huang, K. Shigesada, H.-J. Wee, P. P. Liu, M. Osato, and Y. Ito Molecular basis for a dominant inactivation of RUNX1/AML1 by the leukemogenic inversion 16 chimera Blood, April 15, 2004; 103(8): 3200 - 3207. [Abstract] [Full Text] [PDF] S. S. Kadkol, A. Bruno, C. Dodge, V. Lindgren, and F. Ravandi Comprehensive Analysis of CBF{beta}-MYH11 Fusion Transcripts in Acute Myeloid Leukemia by RT-PCR Analysis J. Mol. Diagn., February 1, 2004; 6(1): 22 - 27. [Abstract] [Full Text] M. Kundu, A. Chen, S. Anderson, M. Kirby, L. Xu, L. H. Castilla, D. Bodine, and P. P. Liu Role of Cbfb in hematopoiesis and perturbations resulting from expression of the leukemogenic fusion gene Cbfb-MYH11 Blood, September 18, 2002; 100(7): 2449 - 2456. [Abstract] [Full Text] [PDF] C. Schoch, A. Kohlmann, S. Schnittger, B. Brors, M. Dugas, S. Mergenthaler, W. Kern, W. Hiddemann, R. Eils, and T. Haferlach Acute myeloid leukemias with reciprocal rearrangements can be distinguished by specific gene expression profiles PNAS, July 23, 2002; 99(15): 10008 - 10013. [Abstract] [Full Text] [PDF] G. Lacaud, L. Gore, M. Kennedy, V. Kouskoff, P. Kingsley, C. Hogan, L. Carlsson, N. Speck, J. Palis, and G. Keller Runx1 is essential for hematopoietic commitment at the hemangioblast stage of development in vitro Blood, June 28, 2002; 100(2): 458 - 466. [Abstract] [Full Text] [PDF]

	Copyright © 2001 by American Society of Hematology         Online ISSN: 1528-0020