BAX belongs to key mediators of cytotoxicity triggered by the combination of VEN and A1155463 in BIM-deficient lymphoma and leukemia cells. (A) Western blot analysis of selected BCL2 family proteins in the tested lymphoma and leukemia cell lines. (B) Western blot confirmation of absence of BIM and/or BAK proteins in the HBL-2 and MAVER-1 lymphoma cell clones with K/O of BIM and BAK genes. (C) K/O of BIM in lymphoma cell lines (HBL-2 and MAVER-1 BIM K/O clones) resulted in increased VEN-R, whereas sensitivity to the combination was largely retained; sensitivity of wild-type (WT) cells is shown for comparison. (D) Immunoprecipitations (IPs) of 2 BIM-deficient cell lines (MINO and Z-138) exposed for 3 hours to A1155463 (1000 nM) or medium only with anti–BCL-XL and anti-BCL2 antibodies and subsequent western blot detection of BAX and BAK proteins bound on BCL-XL and BCL2. (E) Western blot confirmation of absence of BAX protein expression in HBL-2 cell clone with K/O of BAX gene. (F) Apoptosis essays after exposure to the defined VEN and A1155463 concentrations reveal that HBL-2 cells with BAX K/O are significantly more resistant to VEN and to the VEN + A1155463 combination than HBL-2 cells with BAK K/O.