Intraclonal kinetic differences in CLL fractions defined by CXCR4 and CD5. (A–D) Contour plots of CLL cells on the basis of CXCR4 and CD5 levels. An inverse relationship giving a crescent shape is clear in ∼35% of analyses (A), evident in ∼50% (B), suggested in ∼10% (C) and absent in a few patients (D). (E) Representative example of 2H2O enrichment in plasma (CLL875) of patients drinking 2H2O. CLL cells were flow-sorted on the basis of CXCR4 and CD5 densities at time points indicated by arrows. The vertical dashed line indicates end of 2H2O consumption. (F) Average fraction of 2H-labeled cells in the three fractions defined by CXCR4/CD5 densities. *CXCR4dimCD5bright fraction contains significantly higher levels of 2H-labeled DNA compared with CXCR4intCD5int and CXCR4brightCD5dim fractions (P < 0.01 for both). (G) Plot indicates the ratio of 2H-labeled cells in CXCR4dimCD5bright over CXCR4brightCD5dim fractions, indicating that CXCR4dim CD5bright cells proliferated ∼11 times more than CXCR4brightCD5dim cells (*P < 0.0001), (H, I) CXCR4dimCD5bright fractions are significantly enriched in cells expressing Ki-67 (H) and MCM6 (I) compared with CXCR4intCD5int and CXCR4brightCD5dim fractions (*P < 0.01 for both).