Effects of PKC412 and AMN107 on proliferation of HMC-1 cells and BaF/3 cells. (A) Time-dependent effects of PKC412 on ³H-thymidine uptake in HMC-1.2 cells. HMC-1.2 cells were incubated with control medium or PKC412 (300 nM) at 37°C and 5% CO₂ for various time periods as indicated. After incubation,³H-thymidine uptake was measured. Results are expressed as percent of control (³H-thymidine uptake in control medium at each time point) and represent the mean ± SD of triplicates. (B-D) Dose-dependent effects of TK inhibitors on ³H-thymidine uptake in HMC-1 cells. HMC-1.1 cells (•) and HMC-1.2 cells (▪) were incubated in control medium in the absence or presence of various concentrations of either PKC412 (B), AMN107 (C), or imatinib (D) at 37°C for 48 hours. After incubation,³H-thymidine uptake was measured. Results are expressed as percent of control (100%) and represent the mean ± SD from at least 3 independent experiments. (E-F) Effects of PKC412, AMN107, and imatinib on ³H-thymidine uptake in Ton.Kit cells. (E) Ton.Kit.wt cells were kept in IL-3-containing control medium (□) or were induced to express activated wt KIT by adding doxycycline (1 μg/mL) and SCF (in the absence of IL-3; ▪). In both conditions, cells were exposed to either control medium (Co) or various concentrations of PKC412, AMN107, or imatinib, as indicated, for 48 hours (37°C, 5% CO₂). (F) Ton.Kit.D816V.27 cells were kept in control medium (□) or were induced to express KIT D816V by adding doxycycline (1 μg/mL; ▪), and then were exposed to either control medium (Co) or various concentrations of PKC412, AMN107, or imatinib, as indicated, for 48 hours (37°C, 5% CO₂). Thereafter,³H-thymidine uptake was determined. Results are expressed as percent of control (Co) and represent the mean ± SD from 3 independent experiments. ^*P < .05 compared with control.