Fig. 7. Hypothetical model of leukemic cell kinetics in untreated IGHV mutated CLL.

Proposed model of tumor kinetics in CLL that fits the deuterium labeling data in the present study. A proliferative subset of cells transits between PB and lymphoid tissues. These cells become labeled with deuterium, change their phenotype from CXCR4_loCD5_hi to CXCR4_intCD5_int and express high levels of surface BCR. A largely distinct non-proliferating subset is also present. This subset does not label with deuterium, has a CXCR4_hiCD5_lo phenotype and low expression of surface BCR. These cells generally do not migrate into lymphoid tissues but, unlike normal anergic B cells, which undergo apoptosis when excluded from germinal centres, these cells express bcl-2 and so survive.