The Polycomb complex PRC2 supports aberrant self-renewal in a mouse model of MLL-AF9;Nras(G12D) acute myeloid leukemia

Shi, J., Wang, E., Zuber, J., Rappaport, A., Taylor, M., Johns, C., Lowe, S. W., Vakoc, C. R. (2013) The Polycomb complex PRC2 supports aberrant self-renewal in a mouse model of MLL-AF9;Nras(G12D) acute myeloid leukemia. Oncogene, 32 (7). pp. 930-938. ISSN 1476-5594 (Electronic)0950-9232 (Linking)

URL: http://www.ncbi.nlm.nih.gov/pubmed/22469984
DOI: 10.1038/onc.2012.110

Abstract

The Trithorax and Polycomb groups of chromatin regulators are critical for cell-lineage specification during normal development; functions that often become deregulated during tumorigenesis. As an example, oncogenic fusions of the Trithorax-related protein mixed lineage leukemia (MLL) can initiate aggressive leukemias by altering the transcriptional circuitry governing hematopoietic cell differentiation, a process that requires multiple epigenetic pathways to implement. Here we used shRNA screening to identify chromatin regulators uniquely required in a mouse model of MLL-fusion acute myeloid leukemia, which revealed a role for the Polycomb repressive complex 2 (PRC2) in maintenance of this disease. shRNA-mediated suppression of PRC2 subunits Eed, Suz12 or Ezh1/Ezh2 led to proliferation arrest and differentiation of leukemia cells, with a minimal impact on growth of several non-transformed hematopoietic cell lines. The requirement for PRC2 in leukemia is partly because of its role in direct transcriptional repression of genes that limit the self-renewal potential of hematopoietic cells, including Cdkn2a. In addition to implicating a role for PRC2 in the pathogenesis of MLL-fusion leukemia, our results suggest, more generally, that Trithorax and Polycomb group proteins can cooperate with one another to maintain aberrant lineage programs in cancer.Oncogene advance online publication, 2 April 2012; doi:10.1038/onc.2012.110.

Item Type: Paper
Subjects: diseases & disorders > cancer
diseases & disorders
organism description > animal
diseases & disorders > cancer > cancer types > leukemia
organism description > animal > mammal > rodent > mouse
diseases & disorders > cancer > cancer types
CSHL Authors:
Communities: CSHL Cancer Center Program > Gene Regulation and Cell Proliferation
CSHL Cancer Center Shared Resources > Animal Services
CSHL Cancer Center Shared Resources > Bioinformatics Service
CSHL Cancer Center Shared Resources > DNA Sequencing Service
CSHL Cancer Center Shared Resources > Flow Cytometry Service
CSHL Cancer Center Shared Resources > Microarray Service
CSHL Cancer Center Shared Resources > Microscopy Service
CSHL labs > Lowe lab
CSHL labs > Vakoc lab
Watson School > Publications
CSHL Cancer Center Shared Resources > Functional Genomics and Genetics Service
Depositing User: Matt Covey
Date: 2013
Date Deposited: 23 Jan 2013 21:50
Last Modified: 30 Oct 2015 20:44
PMCID: PMC4102143
Related URLs:
URI: http://repository.cshl.edu/id/eprint/27043

Actions (login required)

Administrator's edit/view item Administrator's edit/view item
CSHL HomeAbout CSHLResearchEducationNews & FeaturesCampus & Public EventsCareersGiving