Fig. 4

DT2216 combined with ABT199 synergistically reduced blood engraftment and improved survival in a PDX model.a Illustration of the experimental design of the first study on DFTL-28776 PDX xenograft model. b Changes in blood DFTL-28776 PDX cell burden over time after the start of treatment as shown in a. Data are presented as mean ± SEM (n = 5 for VEH and n = 4 for other groups at the start of treatment). c Survival curve showing the survival of mice after the TCL PDX cell engraftment. Median survival time within each treatment group is presented along with statistical analysis results (n = 5 for VEH and n = 4 for other groups at the start of treatment). *p < 0.05 and **p < 0.01 in indicated comparisons; ns, not significant. The orange line indicates a calculated additive model, with 95% confidence intervals indicated as a yellow shaded range. p value of synergy of DT2219 + ABT199 over additivity: 0.020. d Immunoblot analysis of Bcl-xL, Bcl-2, and Mcl-1 in the spleen (n = 3 mice in each group). Proteins were extracted from the spleens of mice after euthanization when they reached the experimental endpoint as described in the “Materials and methods” section. e–g Quantification of Bcl-xL, Bcl-2, and Mcl-1 levels in d. The data presented are mean ± SEM (n = 3 mice per each group). a, b, and c, p < 0.05 vs. VEH, DT2216, and ABT199, respectively. h Body weight changes over time in DFTL-28776 PDX cell-bearing mice after DT2216 and/or ABT199 treatment as shown in Fig. 5. The data presented are mean ± SEM (n = 5 for VEH and n = 4 for other groups at the start of treatment)