Journal
SCIENCE
Volume 333, Issue 6043, Pages 765-769Publisher
AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/science.1201662
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Funding
- Leukemia Lymphoma Society
- Empire State Stem Cell Scholar award
- Clinical Scholars award
- Starr Foundation
- NIH [GM62437]
- Gabrielle's Angel Foundation
- Acylin Therapeutics Inc.
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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.
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