Fig. 5
Effects of ABT-199, DEX, and DAS on BCR-ABL + ALL primografts. a Patient-derived P564 (left), R610 (middle), and L4967 (right) cells were plated 24 h prior to drug treatment onto primary MSCs. Co-cultures were treated with increasing concentrations of ABT-199, DEX, and DAS alone or in combination with fixed ratios. Fluorescence microscopic analysis of Calcein AM/PI/DAPI staining was performed to determine apoptotic cell death. Quantification of viable cells by counting viable and apoptotic cells in three representative microscopic pictures per well in triplicates. Values are expressed as means ± SD (n = 3). CI values were calculated using the Chou Talalay method. P564 CI(ABT/DEX/DAS) = 0.126; R610 CI(ABT/DEX/DAS) = 0.099. L4967 (CI/ABT/DEX/DAS) = 0.112. b BV173 and patient-derived P564, R610 and L4967 cells (primografts on MSCs) were pretreated with DEX and DAS for 48 h before ABT-199 application for 3 h and mitochondrial staining with TMRE. Decrease in TMRE MFI is expressed as means ± SD (n = 3) as compared to untreated controls set 100%. p-values were calculated by Student’s t-test (*p < 0.05; ***p < 0.001). c NSG recipients received 1 × 106 P564, L4967, and L4951 PDX cells intravenously and survival of control and triple combination treated mice (ABT-199 (20 mg/kg), DEX (1 mg/kg) and DAS (10 mg/kg) by oral gavaging 5 days per week) is shown. d Tumor cell kinetics was monitored by human CD45 expression in peripheral blood cells (P564 and L4967). Note that all control mice engrafted with L4967 cells died before the time of analysis at 4 weeks
