|
|
Prepublished online as a Blood First Edition Paper on December 5, 2002; DOI 10.1182/blood-2002-06-1656.
Submitted June 5, 2002
Accepted October 30, 2002
Role of the WT1 Tumor Suppressor in Murine Hematopoiesis
Julia A Alberta, Gregory M Springett, Helen Rayburn, Thomas A Natoli, Janet Loring, Jordan A Kreidberg, and David Housman*
Center for Cancer Research, Massachusetts Institute of Technology, Cambridge, MA, USA
Medicine, Children's Hospital, Boston, MA, USA; Pediatrics, Harvard Medical School, Boston, MA, USA
Whitehead Institute, Massachusetts Institute of Technology, Cambridge, MA, USA
Center for Cancer Research, Massachusetts Institute of Technology, Cambridge, MA, USA; Biology, Massachusetts Institute of Technology, Cambridge, MA, USA
* Corresponding author; email: dhousman{at}mit.edu.
The WT1 tumor suppressor gene has been found to be expressed by many acute myeloid leukemias. Inhibition of this expression can lead to the differentiation and reduced growth of both leukemia cells and cell lines suggesting that WT1 participates in regulating the proliferation of leukemic cells. However, the role of WT1 in normal hematopoiesis is not well understood. To investigate this question, we have used murine cells in which the WT1 gene has been inactivated by homologous recombination. We have found that cells lacking WT1 show deficits in hematopoietic stem cell function. Embryonic stem cells lacking WT1, while contributing efficiently to other organ systems, make only a minimal contribution to the hematopoietic system in chimeras indicating that hematopoietic stem cells lacking WT1 compete poorly with normal stem cells. In addition fetal liver cells lacking WT1 have an approximately 75% reduction in BFU-E, CFU-E, & CFU-GEMM colony-forming ability. However, transplantation of fetal liver hematopoietic cells lacking WT1 will repopulate the hematopoietic system of an irradiated adult recipient in the absence of competition. We conclude that the absence of WT1 in hematopoietic cells leads to functional defects in growth potential that may be of consequence to leukemic cells which have alterations in the expression of WT1.
 CiteULike  Connotea  Del.icio.us  Digg  Reddit  Technorati What's this?
This article has been cited by other articles:
|
|
|
|
 
K. M. Kirschner, P. Hagen, C. S. Hussels, M. Ballmaier, H. Scholz, and C. Dame
The Wilms' tumor suppressor Wt1 activates transcription of the erythropoietin receptor in hematopoietic progenitor cells
FASEB J,
August 1, 2008;
22(8):
2690 - 2701.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
K. M. Kirschner, N. Wagner, K.-D. Wagner, S. Wellmann, and H. Scholz
The Wilms Tumor Suppressor Wt1 Promotes Cell Adhesion through Transcriptional Activation of the {alpha}4integrin Gene
J. Biol. Chem.,
October 20, 2006;
281(42):
31930 - 31939.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
Y. Rong, L. Cheng, H. Ning, J. Zou, Y. Zhang, F. Xu, L. Liu, Z. Chang, and X.-Y. Fu
Wilms' Tumor 1 and Signal Transducers and Activators of Transcription 3 Synergistically Promote Cell Proliferation: A Possible Mechanism in Sporadic Wilms' Tumor
Cancer Res.,
August 15, 2006;
66(16):
8049 - 8057.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. Dame, K. M. Kirschner, K. V. Bartz, T. Wallach, C. S. Hussels, and H. Scholz
Wilms tumor suppressor, Wt1, is a transcriptional activator of the erythropoietin gene
Blood,
June 1, 2006;
107(11):
4282 - 4290.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. J. Walter, J. S. Park, R. E. Ries, S. K. M. Lau, M. McLellan, S. Jaeger, R. K. Wilson, E. R. Mardis, and T. J. Ley
Reduced PU.1 expression causes myeloid progenitor expansion and increased leukemia penetrance in mice expressing PML-RAR{alpha}
PNAS,
August 30, 2005;
102(35):
12513 - 12518.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
