For instance, a loss of function mutation of Med12 that leads to dissociation of Cyclin C-CDK8/19 from the core Mediator contributes to chronic lymphocytic leukemia (CLL) pathogenesis by activating NOTCH signaling.16 Interestingly, several cofactors interacting with Med12 in HSPCs are also frequently mutated in leukemia and lymphoma, including P300/CBP, KMT2D, WDR5, and KMD6A,17–19 suggesting that alterations in Med12-dependent enhancer regulation may be a potential pathogenic factor. Here, EP300 is linked to B-cell chronic lymphocytic leukemia.