The Leukemogenicity of AML1-ETO Is Dependent on Site-Specific Lysine Acetylation

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Science  14 Jul 2011:
DOI: 10.1126/science.1201662


The chromosomal translocations found in acute myelogenous leukemia (AML) generate oncogenic fusion transcription factors with aberrant transcriptional regulatory properties. While therapeutic targeting of most leukemia fusion proteins remains elusive, the posttranslational modifications that control their function could be targetable. Here, we report that AML1-ETO, the fusion protein generated by the t(8;21), is acetylated by p300 in leukemia cells isolated from t(8;21) AML patients and 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.