Relationship between IGHV mutation status and ZAP-70 or CD38 in defining the time from diagnosis to initial therapy. Kaplan-Meier curves depict the proportion of untreated CLL patients in the validation cohort (N = 705) from diagnosis to initial therapy. Panels A through D depict the time from diagnosis to initial treatment of patients who have CLL cells that express M-IGHV genes, whereas panels E through H show the time from diagnosis to first treatment of patients with CLL cells use U-IGHV. Panels A and E or B and F show how CD38 can segregate cases that are ZAP-70–negative (ZAP-70⁻) or ZAP-70–positive (ZAP-70⁺), respectively. Panels C and G or D and H show how ZAP-70 can segregate cases that are CD38⁺ or CD38⁻, respectively. The P values were determined using the log-rank test. The symbols represent the time at which patients were censored.