Through BH3 profiling, we demonstrate the predominant dependence of MLLr B-lineage ALL cells on BCL-2, as mitochondrial sensitivity to BCL-2-selective BAD peptide was more potent than BCL-XL-selective HRK, MCL-1-selective NOXA, and non-specific BIM peptide. Here, PMAIP1 is linked to acute lymphoblastic leukemia.