Comparison of JAK/STAT signaling pathways activated by IL-15 or by IL-21 shows remarkable differences. (A) CLL cells from 2 representative cases were stimulated with IL-15 or IL-21 (80 ng/mL) or medium only (CTR) for 10 minutes, lysed in appropriate buffers and analyzed by Western blotting using mAbs specific for tyrosine-phosphorylated (JAK1, JAK3, STAT1, STAT3, and STAT5) or unphosphorylated (STAT1) forms of signal transducer proteins, or for β-actin. (B) CLL cells stimulated by IL-15 for 24 hours show enhanced STAT5 phosphorylation compared with IL-21–treated or untreated cells. (C) Densitometric analysis of Western blots to quantify p-JAK1 and p-JAK3 and p-STAT1, p-STAT3, and p-STAT5 levels following treatment with IL-21 or IL-15. Densitometric measurements of phosphoproteins were normalized to unphosphorylated STAT1 or to β-actin levels, and expressed as fold of increase relative to the untreated control. The mean values (± SD) of 7 different patients and statistical significance are shown.