Quantitative proteomic analysis of EZH2 inhibition in acute myeloid leukemia reveals the targets and pathways that precede the induction of cell death

Abstract

Purpose: Chromosomal translocation of the mixed lineage leukemia (MLL) locus generates fusion proteins that drive acute myeloid leukemia (AML) resulting in atypical histone methyltransferase activity and alterations in the epigenetic regulation of gene expression. Targeting histone regulators, such as Enhancer of Zeste Homologue 2 (EZH2), has shown promise in AML. Profiling differential protein expression following inhibition of epigenetic regulators in AML may help to identify novel targets for therapeutics. Experimental design: Murine models of AML combined with quantitative SILAC analysis were used to identify differentially expressed proteins following inhibition of EZH2 activity using 3..