Genetic inactivation of the polycomb repressive complex 2 in T cell acute lymphoblastic leukemia Academic Article uri icon

Overview

MeSH Major

  • Precursor T-Cell Lymphoblastic Leukemia-Lymphoma
  • Repressor Proteins

abstract

  • T cell acute lymphoblastic leukemia (T-ALL) is an immature hematopoietic malignancy driven mainly by oncogenic activation of NOTCH1 signaling. In this study we report the presence of loss-of-function mutations and deletions of the EZH2 and SUZ12 genes, which encode crucial components of the Polycomb repressive complex 2 (PRC2), in 25% of T-ALLs. To further study the role of PRC2 in T-ALL, we used NOTCH1-dependent mouse models of the disease, as well as human T-ALL samples, and combined locus-specific and global analysis of NOTCH1-driven epigenetic changes. These studies demonstrated that activation of NOTCH1 specifically induces loss of the repressive mark Lys27 trimethylation of histone 3 (H3K27me3) by antagonizing the activity of PRC2. These studies suggest a tumor suppressor role for PRC2 in human leukemia and suggest a hitherto unrecognized dynamic interplay between oncogenic NOTCH1 and PRC2 function for the regulation of gene expression and cell transformation.

publication date

  • January 2012

Research

keywords

  • Academic Article

Identity

Language

  • eng

PubMed Central ID

  • PMC3274628

Digital Object Identifier (DOI)

  • 10.1038/nm.2651

PubMed ID

  • 22237151

Additional Document Info

start page

  • 298

end page

  • 301

volume

  • 18

number

  • 2