Peripheral blood cell telomere length measurements indicate that hematopoietic stem cell turnover is not significantly increased in whole blood and apheresis PLT donors.

BACKGROUND: The telomere length (TEL) of peripheral blood leukocytes (PBLs) can be used to estimate hematopoietic stem cell turnover. The current study investigated whether the repetitive stimulation of the hematopoietic system caused by regular whole blood (WB) and PLT donations would affect PBL TEL. STUDY DESIGN AND METHODS: PBLs were obtained from healthy donors (n=94) with a history of at least 3 years of WB donation (median, 7.7 years; range, 3.0-43.0 years) plus additional apheresis PLT donations. The median (range) numbers of WB and PLT donations were 22.0 (6.0-194.0) and 42.0 (7.0-336.0), respectively. Additionally, samples were obtained from healthy nondonors (n=47). PBL TEL was measured with fluorescence in situ hybridization and flow cytometry (flow-FISH). Flow-FISH results were expressed in molecular equivalents of soluble fluorochrome units (MESF; 1000 MESF=1 kMESF) either as absolute (TEL) or as age-adjusted TEL (DeltaTEL). RESULTS: Donor granulocyte and lymphocyte TELs were 12.6 +/- 0.3 (mean +/- SEM) and 13.2 +/- 0.3 kMESF, respectively. No differences were observed when compared with corresponding nondonor data (granulocytes, 12.5 +/- 0.4 kMESF; lymphocytes, 13.6 +/- 0.5 kMESF). Furthermore, DeltaTEL values did not differ between the two groups and were not different from previously established reference values. In addition, neither donor data for age-adjusted TEL for granulocytes nor DeltaTEL for lymphocytes were correlated with either total years or total numbers of WB and/or PLT donations. CONCLUSION: Long-term WB and PLT donation does not affect PBW TEL as measured by flow-FISH, arguing against a significantly increased stem cell turnover.

Normalization of previously shortened telomere length under treatment with imatinib argues against a preexisting telomere length deficit in normal hematopoietic stem cells from patients with chronic myeloid leukemia.

Telomeres are composed of TTAGGG repeats and associated proteins. In somatic cells, telomere repeats are lost with each cell division, eventually leading to genetic instability and cellular senescence. In previous studies, we described substantial and disease stage-specific telomere shortening in peripheral blood (PB) leukocytes from patients with chronic myeloid leukemia (CML). Here, we sought to determine whether age-adjusted telomere length in PB granulocytes (deltaTEL(gran)) is associated with response to treatment with the selective tyrosine kinase inhibitor imatinib. A total of 517 samples from 206 patients in chronic phase (CP), accelerated phase (AP), and blast crisis (BC) before and up to 706 days after initiation of imatinib therapy (median: 144 days) were analyzed by quantitative fluorescence in situ hybridization of interphase cells in suspension (Flow-FISH); telomere fluorescence was expressed in molecular equivalents of soluble fluorochrome units (MESF). Telomere length in samples from start of treatment up to day 144 was significantly shorter (mean +/- SE; -1.5 +/- 0.3 kMESF) compared to samples from patients treated for more than 144 days (-0.8 +/- 0.3 kMESF, p = 0.035). In patients with repeated measurements, a significant increase in telomere length under treatment was observed. Median telomere length in major remission was found to be significantly longer compared to patients without response to treatment measured either by cytogenetics (n = 246, p < 0.05), interphase FISH (n = 204, p = 0.002), or quantitative RT-PCR (n = 371, p < 0.05). In conclusion, the increase in telomere length under treatment with imatinib reflects a shift from Ph+ to Ph- cells in the PB of patients with CML.