Effect of PI 3-kinase inhibitors on the proliferation of NPM-ALK–transformed cells.

Bcr-Abl–transformed Ba/F3 (A), NPM-ALK–transformed Ba/F3 (B), and parental Ba/F3 cells cultured in the presence of IL-3 (C) were incubated with wortmannin (●, 100 nmol/L; ▴, 300 nmol/L) or with DMSO as control (▪) with daily addition of wortmannin and DMSO. The Bcr-Abl– and NPM-ALK–transformed Ba/F3 cells were cultured without IL-3. The number of viable cells was determined by trypan blue staining at the days indicated. Results are representative of at least 3 independent experiments. (D) PI 3-kinase activity was measured as described in the legend to Figure 2 at the time points indicated in NPM-ALK–transformed Ba/F3 cells treated with 300 nmol/L wortmannin. After 24 hours, wortmannin was readded, and PI 3-kinase activity determined after 2 additional hours. The lower panel shows equal expression of NPM-ALK in all cell lysates tested.