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

Recent studies have demonstrated excessive telomeric shortening in peripher al blood leucocytes of bone marrow transplant (BMT) recipients, This findin g has raised concerns about accelerated haemopoietic ageing that might pred ispose to clonal disorders and late graft failure. We studied the periphera l blood neutrophils and T cells of 14 fully engrafted long-term survivors o f 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 < 0.0 01 and < 0.04. respectively), We found no relationship between degree of shortening and the nucleated cel l 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 st ress that causes this telomere shortening does not necessarily occur at the level of the most primitive haemopoietic stem cell.