Recently, a novel BET-inhibitor, GS-5829, has been pre-clinically tested in CLL, which inhibited key signaling pathways and several oncogenes including MYC, Akt, ERK1/2, NF-κB, and BLK. GS-5829 induced apoptosis of primary CLL cells irrespective of their IGHV mutational status [158]. This evidence concerns the gene MAPK3 and B-cell chronic lymphocytic leukemia.