CXCL12-induced ERK activation is inhibited by anti-CXCR4 mAb and PTX but not the PI3K inhibitor wortmannin in ZAP-70⁺ cells, and inhibition of ERK activation in ZAP-70⁺ CLL cells results in partial inhibition of CXCL12-mediated survival. CLL B cells were pretreated with media (alone), anti-CXCR4 antibody, wortmannin, or PTX prior to CXCL12 treatment. (A) Anti-CXCR4 mAb and PTX inhibit ERK activation, whereas wortmannin was without effect. A representative experiment of 4 is shown. (B) CLL B cells from 3 ZAP-70⁺ and 3 ZAP-70^– CLL patients were pretreated with PD98059 (50 μM for 1 h) prior to the addition of CXCL12 (500 ng/mL) and viability was assessed at 24 hours using annexin V/PI staining. Results are presented as mean ± SEM (Student 2-sample 2-tailed t test; *P < .05).