AML1-ETO rapidly induces acute myeloblastic leukemia in cooperation with the Wilms tumor gene, WT1 - PubMed (original) (raw)

Comparative Study

. 2006 Apr 15;107(8):3303-12.

doi: 10.1182/blood-2005-04-1656. Epub 2005 Dec 27.

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, Haruo Sugiyama

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Comparative Study

AML1-ETO rapidly induces acute myeloblastic leukemia in cooperation with the Wilms tumor gene, WT1

Sumiyuki Nishida et al. Blood. 2006.

Free article

Abstract

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 with AML1-ETO-transduced BM cells from wild-type mice. Most importantly, all of the mice that received a transplant of 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.

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