Figure 6. Combination treatment with IRAK1/4 inhibitor and ABT-737 or vincristine reduces T-ALL burden and prolongs host survival.

(A, B, and C) NSG mice (n = 5/group) were injected i.v. with CCRF-CEM cells (3 × 10⁶). On days 3, 6, and 9, mice were i.p. injected with IRAK1/4 inhibitor (5 mg/kg), ABT-737 (40 mg/kg), or vincristine (0.5 mg/kg). T-ALL cell numbers were determined on day 21 by flow cytometry using anti–human CD7. Panel A shows representative dot plots from BM T-ALL cells. (B and C) T-ALL cell numbers from BM. (A–D) Average T-ALL cell numbers from 5 mice (± SD). *P < 0.05 and **P <0.01 by Student’s t test. (D) Jurkat cells (3 × 10⁶) stably expressing IRAK1 shRNA or control shRNA were injected i.v. into NSG mice (n = 5/group). On days 3, 6, and 9, the mice were treated with ABT-737, and T-ALL cell numbers in BM were determined by flow cytometry. (E) Representative images of spleens collected from each of the different treatment groups. (F) NSG mice (n = 5/group) were injected i.v. with CCRF-CEM cells (3 × 10⁶) and treated with IRAK1/4 inhibitor and ABT-737 alone or together on days 3, 6, and 9. Survival and power values (log-rank test) are shown. **P < 0.01 versus DMSO; P < 0.01 for combination versus IRAK1/4 inhibitor; and P < 0.05 for combination versus ABT-737.