Dual PI3K/MTOR inhibition is effective in PTEN-deficient AKT-activated acute leukemia cells. (A) Exposure of Jurkat cells to NVP-BGT226, NVP-BEZ235 or Rapamycin reveals preferential consecutive dephosphorylation of AKT at T308 as well as S473 for NVP-BGT226. This results in suppression of downstream targets including p-T389 p70S6K, p-S575 ULK1, p-S807/811 RB and cleavage of caspase 3. (B) Dose dilution experiments reveal that NVP-BGT226 as well as NVP-BEZ235 inhibit cellular proliferation in an XTT-based assay. Estimated IC50s, calculated by linear regression dose-effect plots, are provided at the bottom of each graph. (C) Assessment of induction of apoptosis shows a preferential proapoptotic effect of NVP-BGT226 when compared to NVP-BEZ235 in an annexin V-based flow cytometry assay. IC50s are provided at the bottom of each graph.