Other genetic mutations associated with ibrutinib resistance in CLL include del(8p), which leads to TRAIL insufficiency in conjunction with driver mutations in EP300, EIF2A, and MLL2 [33] and novel BTK mutation (BTKT316A) that induces ibrutinib resistance via activating PLCG2 in CLL [31,33]. Here, EP300 is linked to B-cell chronic lymphocytic leukemia.