QUICK SEARCH:   [advanced] Author: Keyword(s):
Home     Help     Feedback     Subscriptions     Archive     Search     Table of Contents

First published online 13 April 2005
doi: 10.1242/dev.01824

This Article Figures Only Full Text Full Text (PDF) All Versions of this Article: dev.01824v1 132/10/2263    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Wildonger, J. Articles by Mann, R. S. Search for Related Content PubMed PubMed Citation Articles by Wildonger, J. Articles by Mann, R. S. Social Bookmarking                         What's this?

The t(8;21) translocation converts AML1 into a constitutive transcriptional repressor

¹ Center for Neurobiology and Behavior, Columbia University Medical School, New York, NY 10032, USA
² Department of Biochemistry and Molecular Biophysics, Columbia University Medical School, New York, NY 10032 USA

^* Author for correspondence (e-mail: rsm10{at}columbia.edu)

Accepted 10 March 2005

The human translocation (t8;21) is associated with 12% of the cases of acute myelogenous leukemia. Two genes, AML1 and ETO, are fused together at the translocation breakpoint, resulting in the expression of a chimeric protein called AML1-ETO. AML1-ETO is thought to interfere with normal AML1 function, although the mechanism by which it does so is unclear. Here, we have used Drosophila genetics to investigate two models of AML1-ETO function. In the first model, AML1-ETO is a constitutive transcriptional repressor of AML1 target genes, regardless of whether they are normally activated or repressed by AML1. In the second model, AML1-ETO dominantly interferes with AML1 activity by, for example, competing for a common co-factor. To discriminate between these models, the effects of expressing AML1-ETO were characterized and compared with loss-of-function phenotypes of lozenge (lz), an AML1 homolog expressed during Drosophila eye development. We also present results of genetic interaction experiments with AML1 co-factors that are not consistent with AML1-ETO behaving as a dominant-negative factor. Instead, our data suggest that AML1-ETO acts as a constitutive transcriptional repressor.

Key words: AML1 (RUNX1), AML1-ETO, MTG8, Lozenge, CBFß, Drosophila eye, RUNX1T1

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    Twitter    What's this?

This article has been cited by other articles:

				D. Osman, V. Gobert, F. Ponthan, O. Heidenreich, M. Haenlin, and L. Waltzer A Drosophila model identifies calpains as modulators of the human leukemogenic fusion protein AML1-ETO PNAS, July 21, 2009; 106(29): 12043 - 12048. [Abstract] [Full Text] [PDF]

				L. Roudaia, M. D. Cheney, E. Manuylova, W. Chen, M. Morrow, S. Park, C.-T. Lee, P. Kaur, O. Williams, J. H. Bushweller, et al. CBF{beta} is critical for AML1-ETO and TEL-AML1 activity Blood, March 26, 2009; 113(13): 3070 - 3079. [Abstract] [Full Text] [PDF]

				C. K. Cheng, L. Li, S. H. Cheng, K. M. Lau, N. P. H. Chan, R. S. M. Wong, M. M. K. Shing, C. K. Li, and M. H. L. Ng Transcriptional repression of the RUNX3/AML2 gene by the t(8;21) and inv(16) fusion proteins in acute myeloid leukemia Blood, October 15, 2008; 112(8): 3391 - 3402. [Abstract] [Full Text] [PDF]

				Y. Choi, K. E. Elagib, L. L. Delehanty, and A. N. Goldfarb Erythroid Inhibition by the Leukemic Fusion AML1-ETO Is Associated with Impaired Acetylation of the Major Erythroid Transcription Factor GATA-1. Cancer Res., March 15, 2006; 66(6): 2990 - 2996. [Abstract] [Full Text] [PDF]