Acly ablation abrogates apoptosis resistance in mutant DP progenitors. (A-B) Phospho ser473-AKT (A) and phospho ser455-ACLY (B) on DN, DP, SP4, and SP8 from preleukemic PTENΔ/Δ mutant or PTENflox2 controls. In mutant mice, carrying the ROSAYFPflox2 reporter, DN, DP, SP4, and SP8 cells are gated on YFP+ cells. Levels of BCL-XL (C-D) and BCL-2 (C,E) in DP cells from controls or mice lacking PTEN, ACLY, or both. (F-G) Bcl-2 relative expression to actin in DP cells (F) and DN (G) sorted from 4 PTENΔ/Δ mutant, 3 ACLYΔ/Δ mutant, 4 PTENΔ/Δ;ACLYΔ/Δ double-mutant mice, or 3 flox controls. (H) H3K27Ac enrichment at the Bcl-2 P1 promoter in 3 PTENΔ/Δ mutant, 3 ACLYΔ/Δ mutant, 3 PTENΔ/Δ;ACLYΔ/Δ double mutants, and flox controls. Data represent percentages of input normalized to the actin promoter. (I-J) Sensitivity of DP cells to dexamethasone ex vivo (I) or in vivo (2 mg/kg per day for 3 consecutive days) (J) in PTENΔ/Δ mutant, ACLYΔ/Δ mutant, PTENΔ/Δ;ACLYΔ/Δ animals or flox controls (including Ptenflox2, Aclyflox2, and Ptenflox2;Aclyflox2 mice). IgG, immunoglobulin G; n.s., not significant; PBS, phosphate-buffered saline.