Pharmacological inhibitors of JAK3 or of MEK kinases block IL-15–mediated proliferative and antiapoptotic effects. (A) CD40-activated CLL cells were cultured in triplicate wells of 96-well plates in the presence of IL-15 (50 ng/mL) and of different concentrations of the MEK inhibitor UO126 or of the JAK3 inhibitor AG490 for 48 hours, and then pulsed with ³H-thymidine (1 μCi [0.037 MBq]/well) for an additional 18 hours of culture. Controls using the maximal DMSO concentration used as solvent for the inhibitors were also included. (B) Apoptosis was measured by annexin-V/PI staining of CD40-activated CLL cells after 72 hours of culture in the presence or absence of IL-15 (50 ng/mL) with our without AG490 (30 μM) or UO126 (10 μM). (C) CD40-activated CLL cells were left untreated or treated with IL-21 (50 ng/mL) for 72 hours in the presence or absence of AG490 (30 μM), UO126 (10 μM), or JAK-inhibitor I (0.2 to 0.6 μM) and apoptosis was detected by annexin-V/PI staining. Error bars represent SD.