Pepducins targeting the i1 and i3 loop of CXCR4 inhibit CXCL12-mediated chemotaxis of leukemia and lymphoma cells. (A) CXCR4 surface expression on human leukemia (Jurkat and CEM) and lymphoma (Raji and Ramos) cell lines was analyzed by flow cytometry using PE-conjugated CXCR4 Ab. (B) Inhibition of CXCR4-ERK activation by i1- and i3-derived CXCR4 pepducins. Lysates from Jurkat cells untreated (veh) or treated as indicated before CXCL12 stimulation were immunoblotted with anti–phospho-ERK or total ERK. (C) Human leukemia and lymphoma cells were treated with 0.3-10μM PZ-218 or PZ-210 and chemotaxis to 30nM CXCL12 was determined by microscopically measuring the distance migrated by cells through a cellulose nitrate filter. Chemotaxis of vehicle-treated cells to CXCL12 was set at 100%, and random chemotaxis (chemotaxis of cells in the absence of CXCL12) was set at 0%. Data are presented as the means ± SEM of triplicate experiments with n = 3 for each experiment. *P < .05 and **P < .01 compared with vehicle-treated controls.