IWASAKI Masayuki
   Department   Research Institutes and Facilities, Research Institutes and Facilities
   Position   Assistant Professor
Article types Original article
Language English
Peer review Peer reviewed
Title Epigenetic roles of MLL oncoproteins are dependent on NF-κB.
Journal Formal name:Cancer cell
Abbreviation:Cancer Cell
ISSN code:18783686/15356108
Domestic / ForeginForegin
Volume, Issue, Page 24(4),pp.423-37
Author and coauthor Kuo Hsu-Ping, Wang Zhong, Lee Dung-Fang, Iwasaki Masayuki, Duque-Afonso Jesus, Wong Stephen H K, Lin Chiou-Hong, Figueroa Maria E, Su Jie, Lemischka Ihor R, Cleary Michael L
Publication date 2013/10
Summary 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.
DOI 10.1016/j.ccr.2013.08.019
PMID 24054986