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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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Blood, 1 October 2002, Vol. 100, No. 7, pp. 2449-2456
HEMATOPOIESIS
Role of Cbfb in hematopoiesis 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
From the Genetics and Molecular Biology Branch and
Genetic Disease Research Branch, National Human Genome Research
Institute, National Institutes of Health, Bethesda, MD, and Program in
Gene Function and Expression, University of Massachusetts Medical
School, Worcester.
Core-binding factor  (CBF) and CBF 2 form a
heterodimeric transcription factor that plays an important role in
hematopoiesis. The genes encoding either CBF or CBF2 are involved
in chromosomal rearrangements in more than 30% of cases of acute
myeloid leukemia (AML), suggesting that CBF and CBF2 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 Cbf in hematopoietic
cells. In midgestation embryos, Cbf 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
Cbfb is essential for the generation of hematopoietic stem
and progenitor cells. In adult mice, Cbf was expressed in stem
and progenitor cells, as well as mature myeloid and lymphoid
cells. Although it was expressed in erythroid progenitors, Cbf was
not expressed during the terminal stages of erythropoiesis. Our data
indicate that Cbfb is required for myeloid and lymphoid
differentiation; but does not play a critical role in erythroid differentiation.
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