Fig. 2

Pharmacological restoration of the epigenetic balance of gene expression in human cancers. a MLL translocation and SEC promote the leukemogenesis in MLL-rearranged leukemia. Enhancing the wild-type MLL1 recruitment to chromatin by hijacking the IL1/IRAK4 and CKII/tasapse1 pathways displaces the MLL chimera and SEC and inhibits leukemogenesis. b MLL3 mutation in the PHD leads to the loss of function of MLL3/COMPASS and decreased enhancer H3K4 methylation. EZH2 inhibition by small molecules (e.g., GSK-126) inhibits EZH2 enzymatic activity and decreases H3K27 methylation to restore the tumor suppressor gene expression. c H3K27M mutation leads to the global increase of H3K27 acetylation and aberrant gene expression. Inhibition of BRD4 by small molecules (e.g., JQ-1) displaces the protein from chromatin and restores the normal-like gene expression and inhibits DIPG from progression