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

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 2 form a heterodimeric transcription factor that plays an important role in hematopoiesis. The genes encoding either CBFß or CBF 2 are involved in chromosomal rearrangements in over 30% of cases of acute myeloid leukemia, suggesting that CBFß and CBF 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.

CiteULike Connotea Del.icio.us Digg Reddit Technorati What's this?
This article has been cited by other articles:

|
 |

|
 |
 
A. Pulsoni, S. Iacobelli, M. Bernardi, M. Borgia, A. Camera, N. Cantore, F. Di Raimondo, P. Fazi, F. Ferrara, F. Leoni, et al.
M4 acute myeloid leukemia: the role of eosinophilia and cytogenetics in treatment response and survival. The GIMEMA experience
Haematologica,
July 1, 2008;
93(7):
1025 - 1032.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
Y.-H. Kuo, R. M. Gerstein, and L. H. Castilla
Cbf{beta}-SMMHC impairs differentiation of common lymphoid progenitors and reveals an essential role for RUNX in early B-cell development
Blood,
February 1, 2008;
111(3):
1543 - 1551.
[Abstract]
[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]
|
 |
|

|
 |

|
 |
 
J. Markus, M. T. Garin, J. Bies, N. Galili, A. Raza, M. J. Thirman, M. M. Le Beau, J. D. Rowley, P. P. Liu, and L. Wolff
Methylation-Independent Silencing of the Tumor Suppressor INK4b (p15) by CBF{beta}-SMMHC in Acute Myelogenous Leukemia with inv(16)
Cancer Res.,
February 1, 2007;
67(3):
992 - 1000.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
L. Talebian, Z. Li, Y. Guo, J. Gaudet, M. E. Speck, D. Sugiyama, P. Kaur, W. S. Pear, I. Maillard, and N. A. Speck
T-lymphoid, megakaryocyte, and granulocyte development are sensitive to decreases in CBF{beta} dosage.
Blood,
January 1, 2007;
109(1):
11 - 21.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
M. Wunderlich, O. Krejci, J. Wei, and J. C. Mulloy
Human CD34+ cells expressing the inv(16) fusion protein exhibit a myelomonocytic phenotype with greatly enhanced proliferative ability
Blood,
September 1, 2006;
108(5):
1690 - 1697.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
J. D. Growney, H. Shigematsu, Z. Li, B. H. Lee, J. Adelsperger, R. Rowan, D. P. Curley, J. L. Kutok, K. Akashi, I. R. Williams, et al.
Loss of Runx1 perturbs adult hematopoiesis and is associated with a myeloproliferative phenotype
Blood,
July 15, 2005;
106(2):
494 - 504.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
T. M. Doherty, L. A. Fitzpatrick, D. Inoue, J.-H. Qiao, M. C. Fishbein, R. C. Detrano, P. K. Shah, and T. B. Rajavashisth
Molecular, Endocrine, and Genetic Mechanisms of Arterial Calcification
Endocr. Rev.,
August 1, 2004;
25(4):
629 - 672.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
R. B. Lorsbach, J. Moore, S. O. Ang, W. Sun, N. Lenny, and J. R. Downing
Role of RUNX1 in adult hematopoiesis: analysis of RUNX1-IRES-GFP knock-in mice reveals differential lineage expression
Blood,
April 1, 2004;
103(7):
2522 - 2529.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
F.-Q. Li, R. E. Person, K.-I. Takemaru, K. Williams, K. Meade-White, A. H. Ozsahin, T. Gungor, R. T. Moon, and M. Horwitz
Lymphoid Enhancer Factor-1 Links Two Hereditary Leukemia Syndromes through Core-binding Factor {alpha} Regulation of ELA2
J. Biol. Chem.,
January 23, 2004;
279(4):
2873 - 2884.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
K. E. Elagib, F. K. Racke, M. Mogass, R. Khetawat, L. L. Delehanty, and A. N. Goldfarb
RUNX1 and GATA-1 coexpression and cooperation in megakaryocytic differentiation
Blood,
June 1, 2003;
101(11):
4333 - 4341.
[Abstract]
[Full Text]
[PDF]
|
 |
|
|
|