Loss of MCL-1 enhances killing of MEC04 cells by the BCL-XL inhibitor A-1331852 and sensitizes these cells to high doses of the BCL-2 inhibitor ABT199. (A) MEC04 cells stably expressing Cas9 were infected with doxycycline-inducible sgRNAs targeting either human MCL-1 (isgMCL-1_hEx1) or mouse Bcl2l11(Bim) (nontargeting control) (isgNT). Cells were single cell sorted by flow cytometry following doxycycline treatment and then examined for MCL-1 expression by western blot analysis. Dose-response curves generated from annexin V/PI assays following 24-hour treatment with A-1331852 (B), ABT199 (C), or S63845 (D) at the indicated concentrations. (E) IC50 values generated from dose-response curves were grouped by genotype and compared for each drug treatment. Data are presented as means ± SD of 3 independent experiments, each performed in triplicate (n = 3). Significance was determined by the unpaired Student t test and corrected for multiple comparisons using the Holm-Sidak method. **P < .001.