Effects of WNT inhibition on human T-ALL. (A) Survival of recipient NSG mice after transplantation with xenograft-expanded primary human T-ALL leukemias transduced by lentivirus encoding dnTCF or empty vector control. Leukemia cells were transduced with virus, cultured on MS5-DL1 feeders for 3 days, FACS-sorted for the viral GFP marker, and then injected into each of 4 recipient animals (n = 4) at a dose of 1 × 10⁴ cells per mouse. Results are depicted for 2 different patient leukemias (M71 and F1313) in each experiment. *P < .05; **P < .01 (log-rank test). (B-D) Cell growth as measured by resazurin reduction. Human T-ALL cell lines (HPBALL and RPMI 8402) or PDX tumor cells (M71) were treated in vitro with XAV-939 and/or the γ-secretase inhibitor (GSI) compound E at the doses indicated for 3 to 5 days prior to assay. For the PDX culture, results were normalized against MS5-DL1 feeder-only wells. Mean ± SD values of triplicate assays are plotted. **P < .01; ****P < .0001 (one-way ANOVA). In (D), GSI accounted for 51% of the variation (P < .0001), XAV for 39% of the variation (P < .0001), and their interaction for 3% of the variation (P = .0125) by 2-way ANOVA.