Treatment with MCL-1 inhibitor S63845 following Mnt deletion does not further enhance the survival of mice transplanted with T1 MLL::AF9 AMLs. (A) Treatment protocol. BM cells (Ly5.2) cryopreserved from sick secondary (T1) Mntfl/fl CreERT2/MLL::AF9 or CreERT2/MLL-AF9 mice were transplanted on day 0 into 8-week-old nonirradiated C57BL/6-Ly5.1 syngeneic recipient mice (5 × 105 cells into each of 24 recipients). A total of 12 recipients were treated on days 3, 4, and 5 with TAM (200 mg/kg), and 12 were treated with vehicle (peanut oil). Then, starting on day 6, half of the mice in each treatment arm were injected on 5 consecutive days with the MCL-1 inhibitor S63845 (25 mg/kg) and half were injected with vehicle. The mice were monitored daily for disease symptoms and euthanized humanely when they showed signs of AML-induced stress or at the experiment end point (day 195). (B-E) Kaplan-Meier survival analysis of mice transplanted with T1 MLL::AF9 AMLs of the indicated genotypes and treatments (for T1 AML nomenclature, see Materials and methods and supplemental Table 4).