CG2 and NUP98r AMKL xenografts are sensitive to the induction of the intrinsic apoptotic pathway. (A-B) Dose-response curves and IC₅₀s (supplemental Table 13) determined for each indicated sample of AMKL or AML, submitted to a viability assay in presence of venetoclax or navitoclax. (Cell-Titer Glo, 6-day incubation, 4 replicates). Viability readout was normalized to dimethyl sulfoxide (DMSO) controls for each sample. (C-D) Apoptosis assessed by annexin V staining and flow cytometry of AKML xenografts (mCG2, pdxNTF, and mN5A; n = 2 biological replicates for each cell type), ML2 (AML cell line, n = 2), or normal CB CD34⁺ cells (n = 3) treated for 72 hours in culture as triplicates with the indicated BH3 mimetics (123.5 nM, 370 nM, and 10 μM) or DMSO. P values: ∗∗P < .005; ∗∗∗P < .001; ∗∗∗∗P < .0001. (E-F) Mitochondrial superoxide production was assessed by MitoSox staining and flow cytometry of AMKL xenografts or normal CB CD34⁺ cells, treated with the indicated BH3 mimetics or DMSO for 72 hours in culture in duplicates. Staurosporine (STS) was used as positive control at 1 μM. mAMKL, synthetic xenograft of AMKL; mAML, synthetic xenograft of AML; pdx, patient-derived xenograft; CB CD34⁺, CB CD34⁺ cells.