CG2 AMKL is impaired by navitoclax and DT2216 treatment in vivo. (A) Workflow of experimental procedures to assess the in vivo activity of navitoclax or DT2216 in CBFA2T3::GLS2 (mCG2-1) AMKL xenografts. On the day of euthanizing, (B) spleen weights, (C) percentage of leukemic blasts in the peripheral blood (% GFP⁺hCD45⁺), and (D) infiltration of the BM and spleen (% GFP⁺ cells) were assessed in mice that received transplantation after treatment with either vehicle only (n = 5) or navitoclax (n = 6) for 3 weeks. For comparison, spleen weights of healthy mice that did not receive transplantation (n = 6) were recorded for data shown in panel B. (E) Hematoxylin and eosin–stained longitudinal sections of the tibia and spleen collected from mice on the day of euthanizing. Conditions were as follows: transplantation with CG2 but not treated (leukemic), transplantation and treated with vehicle only (Vehicle), no transplantation and untreated, age-matched littermates of treatment groups (not transplanted), or transplantation and treated with navitoclax (Navitoclax). (F) Leukemic burden (% GFP hCD45⁺) was monitored during treatment in the blood of Vehicle- and navitoclax–treated mice. (G) Kaplan-Meier survival curves of mice that received transplantation with mCG2-1 treated either with vehicle or navitoclax. Log-rank Mantel-Cox test was used to determine survival benefit. (H) Leukemic burden (GFP⁺hCD45⁺) was monitored by bleeding in mCG2-1 vehicle-treated mice vs DT2216-treated mice. (I) Kaplan-Meier survival curves of mCG2-1 AMKL model treated either with vehicle or DT2216. Survival benefit was determined with log-rank Mantel-Cox test. P values: ∗P < .05; ∗∗P < .005; ∗∗∗P < .001; ∗∗∗∗P < .0001.