Telomere biology in hematopoiesis and stem cell transplantation

Abstract

Telomeres are long (TTAGGG)(n) nucleotide repeats and an associated protein complex located at the end of the chromosomes. They shorten with every cell division and, thus are markers for cellular aging, senescence, and replicative capacity. Telomere dysfunction is linked to several bone marrow disorders, including dyskeratosis congenita, aplastic anemia, myelodysplastic syndrome, and hematopoietic malignancies. Hematopoietic stem cell transplantation (HSCT) provides an opportunity in which to study telomere dynamics in a high cell proliferative environment. Rapid telomere shortening of donor cells occurs in the recipient shortly after HSCT; the degree of telomere attrition does not appear to differ by graft source. As expected, telomeres are longer in recipients of grafts with longer telomeres (e.g., cord blood). Telomere attrition may play a role in, or be a marker of, long term outcome after HSCT, but these data are limited. In this review, we discuss telomere biology in normal and abnormal hematopoiesis, including HSCT.

Figure 1:

A model for telomere dynamics and outcomes after hematopoietic stem cell transplantation (HSCT). Relative telomere length is shown on the Y-axis and relative time is on the X-axis. After infusion of donor hematopoietic stem cells (HSC), rapid telomere length attrition occurs then levels off to relatively normal, age-related rates. Critically short telomeres may occur earlier in HSCT recipients.

Figure 2:

Factors that may affect telomere length in HSCT recipients. Telomeres are sensitive to oxidative stress and DNA damage. Telomere length is associated with many factors, including age, genetics, and environmental exposures. Abbreviations: HSCT, hematopoietic stem cell transplantation; GvHD, graft versus host disease