|
|
Blood, 15 April 2006, Vol. 107, No. 8, pp. 3303-3312.
Prepublished online as a Blood First Edition Paper on December 27, 2005; DOI 10.1182/blood-2005-04-1656.
 Previous Article | Next Article 
Submitted April 27, 2005
Accepted November 27, 2005
AML1-ETO rapidly induces acute myeloblastic leukemia in cooperation with Wilms' tumor gene, WT1
Sumiyuki Nishida, Naoki Hosen, Toshiaki Shirakata, Keisuke Kanato, Masashi Yanagihara, Shin-ichi Nakatsuka, Yoshihiko Hoshida, Tsutomu Nakazawa, Yukie Harada, Naoya Tatsumi, Akihiro Tsuboi, Manabu Kawakami, Yoshihiro Oka, Yusuke Oji, Katsuyuki Aozasa, Ichiro Kawase, and Haruo Sugiyama*
Department of Molecular Medicine, Osaka University Graduate School of Medicine, Suita, Osaka, Japan
Department of Functional Diagnostic Science, Osaka University Graduate School of Medicine, Suita, Osaka, Japan
Department of Pathology, Osaka University Graduate School of Medicine, Suita, Osaka, Japan
Department of Cancer Immunotherapy, Osaka University Graduate School of Medicine, Suita, Osaka, Japan
* Corresponding author; email: sugiyama{at}sahs.med.osaka-u.ac.jp.
AML1-ETO, a chimeric gene frequently detected in acute myelogenous leukemia (AML), inhibits the differentiation of myeloid progenitors by suppressing genes associated with myeloid differentiation and increases the replating ability of clonogenic myeloid progenitors. However, AML1-ETO alone cannot induce AML and thus additional genetic events are required for the onset of AML. The Wilms' tumor gene (WT1), which has been identified as the gene responsible for Wilms' tumor, is expressed at high levels in almost all human leukemias. In this study, we have generated transgenic mice (WT1-Tg) that overexpress WT1 in hematopoietic cells to investigate the effects of WT1 on AML1-ETO-associated leukemogenesis. AML1-ETO-transduced bone marrow (BM) cells from WT1-Tg mice exhibited inhibition of myeloid differentiation at more immature stages and higher in vitro colony-forming ability compared to AML1-ETO-transduced BM cells from wild-type mice. Most importantly, all of the mice transplanted with AML1-ETO-transduced BM cells from the WT1-Tg mice rapidly developed AML. These results demonstrate that AML1-ETO may exert its leukemogenic function in cooperation with the expression of WT1.
 CiteULike  Connotea  Del.icio.us  Digg  Reddit  Technorati What's this?
This article has been cited by other articles:
|
|
|
|
 
J. Greiner, L. Bullinger, B.-a. Guinn, H. Dohner, and M. Schmitt
Leukemia-Associated Antigens Are Critical for the Proliferation of Acute Myeloid Leukemia Cells
Clin. Cancer Res.,
November 15, 2008;
14(22):
7161 - 7166.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
P. Paschka, G. Marcucci, A. S. Ruppert, S. P. Whitman, K. Mrozek, K. Maharry, C. Langer, C. D. Baldus, W. Zhao, B. L. Powell, et al.
Wilms' Tumor 1 Gene Mutations Independently Predict Poor Outcome in Adults With Cytogenetically Normal Acute Myeloid Leukemia: A Cancer and Leukemia Group B Study
J. Clin. Oncol.,
October 1, 2008;
26(28):
4595 - 4602.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. S. Makki, T. Heinzel, and C. Englert
TSA downregulates Wilms tumor gene 1 (Wt1) expression at multiple levels
Nucleic Acids Res.,
July 1, 2008;
36(12):
4067 - 4078.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
L. F. Peterson, M. Yan, and D.-E. Zhang
The p21Waf1 pathway is involved in blocking leukemogenesis by the t(8;21) fusion protein AML1-ETO
Blood,
May 15, 2007;
109(10):
4392 - 4398.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
