Marked telomere fluctuation of leukocytes during graft-versus-host disease in allogeneic stem cell transplantation.

ABSTRACT

Immune dysfunction after allogeneic stem cell transplantation (SCT) is closely associated with cell turnover of lymphocytes and homeostasis of hematopoietic stem cells. Telomeres, repetitive sequences (TTAGGG)n on the end of linear chromosomes, reflect the mitotic history of stem cells. Using telomere fluorescence in situ hybridization (FISH) and flow cytometry (flow-FISH), we measured telomere length in lymphocytes and neutrophils at various intervals to analyze the relationship between telomere length change and clinical features in 5 patients who underwent allogeneic bone marrow transplantation. During the first year after allogeneic stem cell transplantation, a marked fluctuation of telomere length in peripheral blood leukocytes was observed in all recipients, and in 3 patients there was a reduction of telomere length during chronic graft-versus-host disease (GvHD) or during post-transplant lymphoproliferative disorder. The reduction of telomere length during GvHD was evident in lymphocytes and neutrophils, but telomere length in neutrophils tended to recover earlier than that observed in lymphocytes. The rapid reduction of telomere length in leukocytes during GvHD was too extensive to be explained by the end-replication problem, suggesting the presence of a telomerically unstable hematopoietic condition after transplant in vivo.