The leukemogenicity of AML1-ETO is dependent on site-specific lysine acetylation Academic Article uri icon

Overview

MeSH Major

  • Cell Transformation, Neoplastic
  • Core Binding Factor Alpha 2 Subunit
  • E1A-Associated p300 Protein
  • Hematopoietic Stem Cells
  • Leukemia, Myeloid, Acute
  • Lysine
  • Oncogene Proteins, Fusion

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.

publication date

  • August 5, 2011

Research

keywords

  • Academic Article

Identity

Language

  • eng

PubMed Central ID

  • PMC3251012

Digital Object Identifier (DOI)

  • 10.1126/science.1201662

PubMed ID

  • 21764752

Additional Document Info

start page

  • 765

end page

  • 9

volume

  • 333

number

  • 6043