Efficacy of BMS-214662 against Ph⁺ leukemic cells versus Ph⁻ non-leukemic cells. (A) Concentration response curve for BMS-214662 against CD34⁺ CML (n = 3) and normal cells (n = 3). The IC₅₀ was approximately 62.5 nM in CD34⁺ CML cells and 250 nM in normal CD34⁺ cells as assessed by total viable cell counts. (B) Concentration response curve for BMS-214662 against parental and WT p210^BCR-ABL Ba/F3 cell lines as assessed by total viable cell counts. The IC₅₀ was approximately 125 nM against WT p210^BCR-ABL Ba/F3 cells and not reached at a concentration of 1000 nM in parental Ba/F3 cells. Data represent the mean of 3 independent experiments. (C) Line graphs showing the results of synergism experiments with BMS-214662 62.5 nM in combination with IM (dose range 0-20 μM) or dasatinib (dose range 0-600 nM) in CD34⁺ normal and CML cells. The graph illustrates the cytotoxic effect of BMS-214662 62.5 nM as a single agent in CD34⁺ CML cells compared with normal CD34⁺ cells as assessed by total viable cell counts and also the added cytotoxicity of using BMS-214662 in combination with either IM or dasatinib. (D) CI plots calculated using CalcuSyn software for BMS-214662 and IM in an algebraic estimate. Combination of BMS-214662 plus IM indicated synergistic activity (CI values < 1) in CD34⁺ CML cells. CI values are represented by points below the dotted line. (E) A conservative isobologram for CD34⁺ CML cells indicated synergism between the 2 drugs.