Changes in telomere length and telomerase activity over time. B cells were purified from PBMCs of 12 B-CLL patients, stored frozen at 2 or more time points during the course of their disease, and subjected to analysis of telomere length by Flow-FISH. (A-B) Changes in mean telomere length in 6 patients from the unmutated subgroup (A) and 6 patients from the mutated subgroup (B). (D-E) Changes in telomerase activity in the same (matched symbols) sets. The rate of change in telomere length and telomerase activity (slope) in each of the 12 patients was estimated by linear regression. (C,F) Average rate of decline of telomere length (C) or change in telomerase activity (F). Shaded areas indicate the range of standard deviation for the values of the 6 individual cases. The average rate of decline in telomere length was 98 bp/y for patients in the unmutated compared with 111 bp/y for patients in the mutated subgroups. Average rate of change in telomerase activity was 0.21 TPG U/y for the unmutated cells compared with 0.19 TPG U/y for the mutated cells. Neither the rate of decline in telomere length nor the rate of change in telomerase activity differed significantly between the 2 subgroups. (G) Telomere lengths of B cells from 48 healthy donors ranging in age from 15 to 74 years were analyzed using Flow-FISH. The rate of decline in telomere length of the normal B cells was computed to be 22 bp/y.