Venetoclax induces apoptosis of CLL cells independently of p53. (A) In response to DNA damage, the commonly mutated/deleted tumor suppressor p53 initiates apoptosis via the intrinsic apoptosis pathway. (B) TP53 mutation and/or deletion results in defective apoptosis in response to DNA damage and contributes to chemotherapy resistance. (C) Venetoclax inhibits BCL2, thereby inducing apoptosis of CLL cells in a mechanism that Anderson et al demonstrate to be independent of p53 expression/function in vitro and in vivo.