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Prepublished online as a Blood First Edition Paper on May 31, 2002; DOI 10.1182/blood-2002-04-1064.

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2002-04-1064v1
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Submitted April 8, 2002
Accepted May 16, 2002

Role of Cbfb in hematopoeisis and perturbations resulting from expression of the leukemogenic fusion gene, Cbfb-MYH11

Mondira Kundu, Amy Chen, Stacie Anderson, Martha Kirby, LiPing Xu, Lucio H Castilla, David Bodine, and Pu Paul Liu*

National Human Genome Research Institute, Genetics and Molecular Biology Branch, National Institutes of Health, Bethesda, MD, USA
National Human Genome Research Institute, Genetic Diseases Research Branch, National Institutes of Health, Bethesda, MD, USA
Programs in Gene Function and Expression, University of Massachusetts Medical School, Worcester, MA, USA

* Corresponding author; email: pliu{at}nhgri.nih.gov.

CBFß and CBF{alpha}2 form a heterodimeric transcription factor that plays an important role in hematopoiesis. The genes encoding either CBFß or CBF{alpha}2 are involved in chromosomal rearrangements in over 30% of cases of acute myeloid leukemia, suggesting that CBFß and CBF{alpha}2 play important roles in leukemogenesis. Inv(16)(p13;q22) is found in almost all cases of AML M4Eo and results in the fusion of CBFB with MYH11, the gene encoding smooth muscle myosin heavy chain. Mouse embryos heterozygous for a Cbfb-MYH11 knock-in gene lack definitive hematopoiesis, a phenotype shared by Cbfb-/- embryos. In this study we generated a Cbfb-GFP knock-in mouse model to characterize the normal expression pattern of Cbfß in hematopoietic cells. In mid-gestation embryos, Cbfß was expressed in populations enriched for hematopoietic stem cells and progenitors. This population of stem cells and progenitors was not present in mouse embryos heterozygous for the Cbfb-MYH11 knock-in gene. Together, these data suggest that Cbfb-MYH11 blocks embryonic hematopoiesis at the stem/progenitor cell level and that Cbfß is essential for the generation of hematopoietic stem and progenitor cells. In adult mice, Cbfß was expressed in stem and progenitor cells, as well as mature myeloid and lymphoid cells. Although it was expressed in erythroid progenitors, Cbfß was not expressed during the terminal stages of erythropoiesis. Our data indicates that Cbfß is required for myeloid and lymphoid differentiation; but does not play a critical role in erythroid differentiation.


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