PIK-75 induces apoptosis in a manner that is distinct from other inhibitors targeting the PI3K pathway. (A) MV4;11 cells were cultured in the presence of the PI3K inhibitors, A66 (triangle), GDC-0941 (cross), YM-024 (open square), PI-103 (diamond), BEZ-235 (closed circle), and PIK-75 (open circle) for 24 hours and cell survival was determined by flow cytometric enumeration of PI-negative cells. (B) FACS-purified primary human CD34+CD38-CD123+ leukemic stem and progenitor cells were plated in DMSO, 100 nM PIK-75, or the p110β- (1 μM TGX-221), p110δ- (5 μM IC87114), or p110γ- (100 nM AS252424) selective PI3K inhibitors and cell survival examined at 24 hours by annexin V staining. (C) Primary human AML cells were incubated in 1 μM PI-103 or 1 μM PIK-75 for 8 hours following which cell lysates were immunoblotted. (D) MV4;11 cells were treated with 100 nM PIK-75 following which cell lysates were immunoblotted with the indicated antibodies. Results are typical of at least 2 experiments.