Imatinib mesylate markedly inhibits the growth of IL-2–independent p210⁺ NK92 cells, which is reversible by IL-2.

(A) Untransduced (parental) and p210-eGFP⁺(p210⁺) NK92 cells (3 × 10⁵ cells/mL) were cultured for 14 days with or without IL-2 and with or without the addition of 0 (■), 1 (░), or 10 (▪) μM imatinib mesylate. K562 cells were completely inhibited by imatinib mesylate after 7 days of culture. p210⁺ NK92 cells exhibited a dose-dependent decline in growth, and all cells died from 10 μM imatinib mesylate. In contrast, p210⁺ NK92 cells continued to grow despite imatinib mesylate when IL-2 was re-added to cultures, showing that imatinib mesylate's effects are reversible. Imatinib mesylate had no effect on the growth of the parental NK92 cells (negative control). (B) Parental, eGFP⁺, and p210-eGFP–transduced (p210⁺) NK92 cells (1 × 10⁴ cells/100 μL) were treated with imatinib mesylate for 72 hours in the presence or absence of IL-2, and then tested for proliferation using³H-thymidine incorporation. Concentrations of imatinib mesylate are as follows: ■, no imatinib mesylate; ░, 1 μM imatinib mesylate; ▪ 10 μM imatinib mesylate. The IL-2–independent p210⁺ NK92 cells show marked decrease in proliferation from imatinib mesylate when compared with control eGFP⁺ cells (P < .0001), and the addition of IL-2 reversed this effect. Both parental and eGFP⁺ NK92 cells proliferate less in the absence of IL-2, and imatinib mesylate further accelerates this decline, whereas in the presence of IL-2, imatinib mesylate has no effect (P = NS). Each bar shows the mean ± SEM of 12 replicates for each condition.