Epigenetic Roles of MLL Oncoproteins Are Dependent on NF-κB

Overview

Journal Cancer Cell

Publisher Cell Press

Specialty Oncology

Date 2013 Sep 24

PMID 24054986

Citations 57

Authors

Hsu-Ping Kuo

Zhong Wang

Dung-Fang Lee

Masayuki Iwasaki

Jesus Duque-Afonso

Stephen H K Wong

Chiou-Hong Lin

Maria E Figueroa

Jie Su

Ihor R Lemischka

Michael L Cleary

Affiliations

Soon will be listed here.

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.

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