Leukemic-cell birth associates with other poor prognostic factors in CLL patients who carry circulating CXCR4/CD5 leukemic fractions. (A) Cytometry profiles of 2 representative CLL patients with low and high BR illustrating the inverse surface expression of CXCR4 and CD5 in the gating strategy that was used for all of the patients (left). Proposed model of the CLL life cycle, where differential surface densities of CXCR4 and CD5 identify 3 intraclonal fractions from cells that have recently divided and egressed from the lymphoid niche (CXCR4^DimCD5^Bright; PF) to an IF more representative of the bulk CLL clone to older quiescent cells that may be attempting to home back and escape cell death (CXCR4^BrightCD5^Dim; RF) (right). (B) Association of cellular BRs with different CLL prognostic factors, including the requirement of treatment during the study period (0-7 years), IGHV mutational status, and levels of surface ZAP70 or CD38 in the 21 CLL patients studied here. Unpaired nonparametric Mann-Whitney U tests were used to explore differences. Circles represent CLL patients in each clinical subcategory. **P < .01. (C) Kaplan-Meier curves of TTFT for CLL patients stratified according to low or high BR (dichotomized at 0.35% per day). (D) Kaplan-Meier curves of TTFT for CLL patients stratified according to different prognostic factors. P values in panels C and D were determined using the log-rank test.