The leukemogenicity of AML1-ETO is dependent on site-specific lysine acetylation.

Abstract

The chromosomal translocations found in acute myelogenous leukemia (AML) generate oncogenic fusion transcription factors with aberrant transcriptional regulatory properties. Although therapeutic targeting of most leukemia fusion proteins remains elusive, the posttranslational modifications that control their function could be targetable. We found that AML1-ETO, the fusion protein generated by the t(8;21) translocation, is acetylated by the transcriptional coactivator p300 in leukemia cells isolated from t(8;21) AML patients, and that this acetylation is essential for its self-renewal-promoting effects in human cord blood CD34(+) cells and its leukemogenicity in mouse models. Inhibition of p300 abrogates the acetylation of AML1-ETO and impairs its ability to promote leukemic transformation. Thus, lysine acetyltransferases represent a potential therapeutic target in AML.

DOI: 10.1126/science.1201662
020402011201220132014201520162017
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@article{Wang2011TheLO, title={The leukemogenicity of AML1-ETO is dependent on site-specific lysine acetylation.}, author={Lan Wang and Alexander Gural and Xiao-jian Sun and Xinyang Zhao and Fabiana Perna and Gang Huang and Megan A. Hatlen and Ly Vu and Fan Liu and Haiming Xu and Takashi Asai and Hao Xu and Tony R Deblasio and Silvia M Menendez and Francesca Voza and Yanwen Jiang and Philip A. Cole and Jinsong Zhang and Ari Melnick and R. G. Roeder and Stephen D. Nimer}, journal={Science}, year={2011}, volume={333 6043}, pages={765-9} }