The impact of additional inhibition of mTORC2 on combined PI3K and mTORC1 inhibition in B-ALL is independent of the presence of an ABL translocation.

<div><p>BCR-ABL+ (PH and BV) and BCR-ABL- (HP) cells were treated with 0.5µM or 2µM NVP-BKM120 (PI3K inhibitor), 0.5µM or 2µM RAD001 (mTORC1 inhibitor) alone or in combination. For combined PI3K/mTORC1/C2 inhibition, cells were treated with 0.5µM or 2µM of NVP-BGT226 or NVP-BEZ235. (A) Proliferation and (B) cell death were measured after 4 days of drug treatment. </p> <p>(A, B) Cell proliferation was assessed by XTT assay, induction of cell death was measured by Annexin-V/propidium iodide staining. The data shown represent the means + SD of 3 experimental replicates from one representative experiment out of 3 performed. </p> <p>(C) Lysates were prepared after 2h of drug treatment for the detection of phosphorylated and total AKT, S6 and 4E-BP1 by Western blotting. Lysates of untreated Jurkat cells were used as positive controls, those of cells treated for 2h with 1µM Wortmannin (WM) were used as negative controls. β-Actin was used as loading control. </p>