Format

Send to:

Choose Destination
See comment in PubMed Commons below
Cancer Cell. 2013 Oct 14;24(4):423-37. doi: 10.1016/j.ccr.2013.08.019. Epub 2013 Sep 19.

Epigenetic roles of MLL oncoproteins are dependent on NF-κB.

Author information

  • 1Department of Pathology, Stanford University School of Medicine, Stanford, CA 94305, USA.

Abstract

MLL fusion proteins in leukemia induce aberrant transcriptional elongation and associated chromatin perturbations; however, the upstream signaling pathways and activators that recruit or retain MLL oncoproteins at initiated promoters are unknown. Through functional and comparative genomic studies, we identified an essential role for NF-κB signaling in MLL leukemia. Suppression of NF-κB led to robust antileukemia effects that phenocopied loss of functional MLL oncoprotein or associated epigenetic cofactors. The NF-κB subunit RELA occupies promoter regions of crucial MLL target genes and sustains the MLL-dependent leukemia stem cell program. IKK/NF-κB signaling is required for wild-type and fusion MLL protein retention and maintenance of associated histone modifications, providing a molecular rationale for enhanced efficacy in therapeutic targeting of this pathway in MLL leukemias.

Copyright © 2013 Elsevier Inc. All rights reserved.

PMID:
24054986
[PubMed - indexed for MEDLINE]
PMCID:
PMC3816582
Free PMC Article
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Elsevier Science Icon for PubMed Central
    Loading ...
    Write to the Help Desk