Treatment of NPM-ALK expressing cells with an MDM2 inhibitor in combination with either JNK or PI 3-kinase inhibitors sensitizes cells to apoptosis and growth arrest. Induction of apoptosis as determined by the presence of caspase 3/7 in SUDHL-1 cells treated with combinations of 20 μM nutlin-3, 20 μM LY294002, and/or 20 μM SP600125 for 48 (A), 6, or 24 hours (B). Apoptosis was confirmed after Western blot analysis of cell lysates for PARP (C). Cellular proliferation is detected after incorporation of AlamarBlue 48 (D), 6, or 24 (E) hours after treatment of SUDHL-1 cells as indicated above. Percentages of cells in each stage of the cell cycle after treatment with inhibitors for 48 hours as indicated above (F). A representative dataset of triplicate experiments is shown in panels C and F. Error bars in panels A, B, D, and E represent SD of the mean of at least 3 independent experiments.