Loss-of-function screen reveals metabolic vulnerabilities in MLL-AF9–driven AML. (A) Heatmap showing 45 metabolic genes overexpressed in L-GMPs as compared with N-GMPs in the retrovirus-based MLL-AF9 leukemia model.²⁵  (B) Experimental workflow for the genetic depletion screen. (C) Distribution of the number of shRNA-modified L-GMPs per well relative to the number of L-GMPs per control well on the respective plate. Any gene for which ≥3 shRNAs decreased the number of L-GMPs <1.5 standard deviations (SDs) of the mean of L-GMPs in control wells, in technical duplicate, was counted as a hit as long as ≤1 shRNA decreased numbers of N-GMPs <1.5 SDs for the same gene. Aldh3a2, among all sh-RNAs, is shown in red. (D) Number of L-GMPs was decreased <1.5 SDs in 3 wells carrying independent Aldh3a2 shRNAs in the screen.