Figure 1
Gefitinib targets ZAP-70+ CLL cells. (a) Distribution of gefitinib IC50 values in ZAP-70+ (n=22 tested) or ZAP-70− (n=23 tested) patient samples after 24 h of treatment. Only values within tested range of 1–15 μM are shown; values outside tested range were excluded. (b) Percentage of annexin V+ CLL cells from ZAP-70+ or ZAP-70− patients treated for 24 h with 10 μM gefitinib. (c) Percentage of annexin V+ CLL cells from 5 different ZAP-70+ patients after 72 h of treatment with DMSO, and 1, 5, or 10 μM gefitinib. (d) Lysates were collected after 24 h of CLL cells treated with DMSO, 10 μM gefitinib, or 15 μM gefitinib. (e) Western blot with lysates of ZAP-70− and ZAP-70+ lymphoid cell lines compared with ZAP-70− and Syk− HEK293 cell lines. (f) Treatment of lymphoid cell lines with 30 μM gefitinib for 3, 6, and 18 h normalized to DMSO-treated control. Three independent experiments are shown with standard errors (paired t-test). (g) Lymphoid cell lines treated with 0.1 to 30.0 μM gefitinib for 24 h. Cell death analyzed by staining with Annexin V-FITC and 7AAD and analysis by flow cytometry. Three independent experiments are shown with standard errors (paired t-test). *P<0.05, **P<0.01, or ***P<0.001
