PTEN loss activates ACLY in human T-ALL cells to sustain cell growth. (A-C) PTEN, pAKTser473, and pACLYser455 (A-B) and acetyl-CoA levels (C) in human T-ALL cell lines transduced with a lentiviral vector carrying an shRNA PTEN or a control shRNA (shRNA Ctrl A). (D-E) Relative abundance of unlabeled and labeled metabolites mapped to glycolysis (D) and TCA (E) in DND41 cells exposed to [¹³C] glucose for 1 hour, 4 hours, or 24 hours. (F) Growth of DND41, RPMI-8402, and HBP-ALL transduced with a shRNA PTEN, a shRNA ACLY, or the combination of both and relative control shRNA (shRNA Ctrl A as control for the shRNA targeting PTEN and shRNA Ctrl B as control for the shRNA targeting ACLY). (G) Growth of Jurkat cells transduced with an shRNA ACLY or control shRNA in the presence or in the absence of doxycycline (dox)–mediated PTEN re-expression. aKG, α-ketoglutarate; PBS, phosphate-buffered saline; TCA, tricarboxylic acid; Unlab, unlabeled.