Relationship between ZAP-70 and CD38 or IGHV mutation status 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 ZAP-70 (ZAP-70⁺), whereas panels E through H show the time from diagnosis to first treatment of patients with CLL cells that were ZAP-70 negative (ZAP-70⁻). Panels A and E or B and F show how IGHV mutation status can segregate cases that are CD38⁺ or CD38⁻, respectively. Panels C and G or D and H show how CD38 can segregate cases that use U-IGHV or M-IGHV, respectively. The P values were determined using the log-rank test. The symbols represent the time at which patients were censored.