Telomere shortening in leucocyte subsets of long-term survivors of allogeneic bone marrow transplantation

Abstract

Recent studies have demonstrated excessive telomeric shortening in peripheral blood leucocytes of bone marrow transplant (BMT) recipients. This finding has raised concerns about accelerated haemopoietic ageing that might predispose to clonal disorders and late graft failure. We studied the peripheral blood neutrophils and T cells of 14 fully engrafted long-term survivors of BMT. We found that in both neutrophils and T cells there was significant telomere shortening in the recipient (0.6 and 0.5 kb, respectively; P < 0.001 and < 0.04, respectively). We found no relationship between degree of shortening and the nucleated cell dose given at the time of transplant. We also demonstrated significantly longer telomeres in T cells than neutrophils from the same individual (mean 11.6 kb and 10.6 kb, respectively; P=0.0001). We propose mechanisms to account for these observations. The replicative stress that causes this telomere shortening does not necessarily occur at the level of the most primitive haemopoietic stem cell.