Schedules of venetoclax or teriflunomide in relationship to decitabine affect anti-AML efficacy in vivo. (A) Experiment schema evaluating different schedules of venetoclax in relationship to decitabine. NSG mice were tail-vein inoculated with 0.3 × 106 AML cells from a patient with cytarabine- and HMA-refractory AML. Treatments were initiated after confirmation of engraftment to >10% hCD45+ cells in the BM in 3 mice. (B) Time to distress. Mice were euthanized for signs of distress as per the animal protocol. P values from log-rank test. Leukemia burden in the marrow and spleen at time of euthanasia is shown in supplemental Figure 4A-B. (C) Experiment schema evaluating different schedules of teriflunomide in relationship to decitabine. NSG mice were tail-vein inoculated with 1 × 106 AML cells from a patient with TP53-mutated complex cytogenetics AML. Treatments were initiated after confirmation of engraftment to >10% hCD45+ cells in the BM in 3 mice. (D) Time to distress. Mice were euthanized for signs of distress as per the animal protocol. P values from log-rank tests. Leukemia burden in the marrow and spleen at time of euthanasia is shown in supplemental Figure 4B-C. BM, bone marrow; D, decitabine; Dec, decitabine; SC, subcutaneous; Teri, teriflunomide; T, teriflunomide; Ven, venetoclax.
