Clonal heterogeneity in growth kinetics of CD34+CD38- human cord blood cells in vitro is correlated with gene expression pattern and telomere length.

Human hematopoietic stem cells (HSCs) are characterized by an extensive proliferative capacity that decreases from fetal liver to cord blood (CB) to adult bone marrow. In previous studies, it was demonstrated that the proliferative capacity of individual CD34+CD38- HSC clones is correlated with their growth kinetics in vitro and that HSC turnover in vivo can be estimated by telomere-length measurements. The present study was aimed at the characterization of the clonal composition of CD34+CD38- human umbilical CB cells in terms of growth kinetics, telomere length, and gene expression profile.

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).