Fig. 3
Curative pharmacotherapy of BCR-ABL + ALL with ABT-199, dexamethasone and dasatinib. a BV173 cells were stably transduced with lentiviral constructs encoding specific shRNA targeting BIM or a control sequence and treated with various concentrations of dasatinib for 48 h. PI staining was performed to monitor induction of apoptosis. Values are expressed as means ± SD (n = 3). p-values were calculated by Student’s t-test (***p < 0.001). b BV173 cells were treated with ABT-199, DAS, DEX alone or in combination at fixed ratios for 24 h followed by PI staining. Values are expressed as means ± SD (n = 3). Combination indices were calculated using the Chou Talalay method. CI (ABT/DEX) = 0.88, CI (ABT/DAS) = 0.62, CI (ABT/DEX/DAS) = 0.15. c NSG recipients received 1 × 106 BV173 cells intravenously. Tumor proliferation was monitored by using in vivo bioluminescent IVIS assay. Treatment started 1 week after tumor inoculation. Kaplan–Meier survival curves (left) and representative IVIS results for week 1–35 (right) of recipients treated with DEX (1 mg/kg) and DAS (10 mg/kg) or in combination with ABT (constant dose of 20 mg/kg) by oral gavaging 5 days per week are shown. Treatment was stopped after week 7. Data are summarized from three independent experiments. Log-rank test was used for statistical survival analyses (**p ≤ 0.01, ***p ≤ 0.001)
