Ras/mitogen-activated protein kinase (MAPK) and FRAP/mTOR signaling pathways are required for the survival of NPM/ALK-positive cells. (A) NPM/ALK-positive SUDHL-1 cells were incubated with various concentrations of FTI-277 (ras inhibitor), (B) U0126 (p44/42 inhibitor), and (C) rapamycin (mTOR inhibitor) for variable time periods. Cell viability was evaluated by the MTT assay and compared with DMSO-treated control cells. The data represent mean percentage of viability relative to DMSO control obtained from triplicate experiments. Cell cycle analysis was performed as outlined in “Methods.” Representative data obtained from 3 independent experiments are shown. Caspase-3 activity assay was performed as described in “Methods.” U0126 (Calbiochem) was added to SUDHL-1 cells to create a positive (induced apoptosis) control. Z-VAD-FMK inhibitor was used at a final concentration of 50 μM. A negative control was prepared using untreated cells. The data represent the mean values of triplicate measurements. (D) Western blot analyses of drug-treated cells.