MCL-1 inhibitors are less effective in CARF-resistant myeloma cells. (A) Dose-response curves of MCL-1 inhibitors in CARF-sensitive and -resistant RPMI8226 cells (n = 3 biological replicates). Viability was assessed 72 hours after treatment induction. (B) Dose-response curves of MCL-1 inhibitors in IXA-sensitive and -resistant RPMI8226 cells. Viability was assessed 72 hours after treatment induction (n = 3 biological replicates). (C) Baseline Bcl-2 family protein levels in CARF-sensitive and -resistant cell line variants (n = 3 biological replicates). (D) Coimmunoprecipitation experiments in CARF-sensitive (DMSO) and -resistant (CARF) RPMI8226 cells revealed no explanation for the reduced activity of MCL-1 inhibitors (n = 2 biological replicates). *Immunoglobulin light chain. (E) BAK activity status in CARF-sensitive and -resistant cells 4 hours after treatment with MCL-1 inhibitors (n = 3 biological replicates). *P < . 05; **P < .01, ***P < .001; ns, not significant.