Figure 6.

Dexamethasone (DEX) and dasatinib (DAS) act synergistically to induce cell death in T-cell acute lymphoblastic leukemia (T-ALL). (A) Cell viability of parental SUPT1 cells (mock), shCtrl (NTC), shLCK#1 or shLCK#3 transduced SUPT1 cells upon treatment with increasing DEX concentrations (0-1699 nM). (B) Cell viability of SUPT1 with and without DAS (left; black line, no DAS; blue line, 0.8 μM; red line, 2.0 μM) in combination with increasing concentrations of DEX (0-600 nM) as derived from the drug matrix with titration of DEX (0-600 nM) and DAS (0-50 uM; right). (Right) Combenefit analysis of drug matrix demonstrates drug synergy in SUPT1 cells at clinically relevant drug concentrations. (C) (Left) LK203 cells were expanded ex vivo on OP9-DL1 feeder cells for 1 week prior to treatment with and without DAS (black line, no DAS; blue line, 0.08 μM; red line, 2.0 μM; orange line, 10 μM) in combination with increasing concentrations of DEX (0-600 nM) as derived from a drug matrix with DEX (0-600 nM) and DAS (0-50 uM) (Online Supplementary Figure S6E). (Right) Cell death analysis in LK203 cells exposed to control (Ctrl) conditions, DAS (1 μM), DEX (100 nM) or DAS+DEX combination treatment. (D) (Left) Normalized GILZ mRNA expression in Jurkat cells after transduction with shNTC or shLCK#3 with or without DEX exposure (100 nM). (Right) Normalized GILZ mRNA expression in Jurkat cells after exposure to Ctrl conditions, DAS (2 μM), DEX (100 nM) or DAS+DEX combination treatment at the same concentrations. Student's t-test: **P<0.01, ***P<0.005, ****P<0.001.