Therapeutic apoptosis induction by inhibition of MYC and PI3K-AKT pathways in treatment-resistant human T-ALL. (a to d) Effect of BEZ235 (500 nM), JQ1 (1 μM), or both drugs in combination on apoptosis induction in primary human treatment-resistant T-ALL samples treated in short-term culture assays (48 hrs), as assessed using FACS analysis for Annexin V and 7AAD staining. Data for early apoptotic (annexin V-positive, 7AAD-negative) and late apoptotic (annexin V-positive, 7AAD-positive) cells are shown separately, and error bars indicate mean +/− standard error of the mean for each apoptotic subset. P values were calculated using 2-way ANOVA analysis on the combined data for all apoptotic cells (early + late). In all four patient samples, the effects of the drugs were at best additive; no interaction terms were statistically significant at the 0.10 level.