To better assess PI3K inhibitors as a potential therapeutic strategy for T-ALL, we performed comprehensive analyses of PI3K-Akt signaling in T-ALL cells using multiplex, multiparameter flow cytometry with pan- and isoform-specific PI3K inhibitors, tested the effect of candidate compounds to induce cell death and inhibit proliferation, and performed preclinical mouse trials with pan- and γ-isoform-specific PI3K inhibitors. This evidence concerns the gene AKT1 and acute lymphoblastic leukemia.