SOR, ART838, and VEN synergized to inhibit growth and stimulate apoptotic cell death of human AML cell lines, but spared normal human CD34⁺HSPCs. (A) MOLM14 and MV4;11 AML cells were cultured for 48 hours with ART838, VEN, SOR, or SAV using 3 sets of drug concentrations by using 2 twofold dilutions from the approximate IC₅₀ of each drug (in bold) for each cell line.^18,52,53  Graphs plot growth inhibition relative to DMSO, by alamarBlue assays (means of 3 experiments performed with triplicate samples plus or minus SEM). (B) Summary of 3 annexin V/7AAD flow cytometric experiments (mean plus or minus SEM) using MOLM14 and MV4;11 AML cells treated for 18 hours with DMSO, ART838 (200 nM), VEN (50 nM), SOR (5 μM), ART838 plus VEN, ART838 plus SOR, VEN plus SOR, or SAV, with or without QVD. Data points represent percentage of viable (Annexin V⁻/7AAD⁻) cells. (C) Colored symbols are as shown in the keys in panels A and B. Primary human CD34⁺ HSPCs, or MV4;11 AML cells were cultured with drug(s) for 24 hours, then diluted (>100-fold) and 100 to 500 cells plated in 1 mL of semisolid methylcellulose medium (H4434 for HSPCs and H4230 for MV4;11 AML cells; Stem Cell Technologies, Vancouver, Canada). Seven to 14 days later, total (erythroid plus nonerythroid for CD34⁺ HSPCs) colonies (≥20 cells) were enumerated.⁹⁹  Graph summarizes means of 3 independent experiments with triplicate samples plus or minus SEM. Statistical comparisons were for groups cultured with SAV vs single drugs (A) or with each drug vs DMSO (B-D). *P < .05; **P < .01; ***P < .001; no asterisk if P > .05.