BCLXL is the major factor that limits MM cell death to the pharmacological inhibition of MCL1. (A) After transfection with scramble or BCLXL-specific siRNA, MM1S, LP1, and U266 HMCLs were treated with A1210477 (5 μM) for 24 hours, cell death was assessed by Annexin V staining and the induction of apoptosis was compared with the non-treated controls. Results represent the mean ± SD of 5 independent experiments. Statistical analysis was performed using Student t-Test. (B) Combination of A1210477 and A1155463 overcomes A1210477 resistance in LP1 and U266 HMCLs. LP1 and U266 HMCLs were treated with combination of low doses of both A1210477 (3 and 4 μM) and A1155463 (100, 300 and 500 nM). All data points represent the mean of triplicate experiments ± SD. Combination index (CI) was calculated using CalcuSyn software.