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Prepublished online as a Blood First Edition Paper on August 22, 2002; DOI 10.1182/blood-2002-06-1832.
Submitted June 20, 2002
Accepted August 2, 2002
Homeostasis of telomere length rather than telomere shortening after allogeneic peripheral blood stem cell transplantation
Helene Roelofs*, Elmar S de Pauw, Aeilko H Zwinderman, Sonja M Opdam, Roel Willemze, Hans J Tanke, and Willem E Fibbe
Hematology, Leiden University Medical Center, Leiden, The Netherlands
Medical Statistics, Leiden University Medical Center, Leiden, The Netherlands
Molecular Cell Biology, Leiden University Medical Center, Leiden, The Netherlands
* Corresponding author; email: H.Roelofs{at}lumc.nl.
Hematopoietic reconstitution after stem cell transplantation requires excessive replicative activity due to the limited number of stem cells that are used for transplantation. After bone marrow transplantation telomere shortening has been detected in hematopoietic cells. This has been interpreted to result from excessive replication of the stem cells, with putative concomitant reduction of their replicative potential. Nowadays, hematopoietic stem cells from cytokine-mobilized peripheral blood are increasingly used for stem cell transplantation. These grafts contain higher numbers of hematopoietic stem cells, resulting in a faster hematopoietic reconstitution.
We have performed a combined prospective and cross-sectional study of the hematological recovery and the telomere length dynamics in the immediate reconstitution period after allogeneic T cell-depleted blood stem cell transplantation. We analyzed hematological recovery and telomere length of granulocytes, monocytes, B cells and T cell subsets in 30 donor/recipient combinations. We found fast recovery in combination with a transient telomere shortening in the myeloid lineages. This initial reduction of telomere length was followed by an increase in telomere length, to such an extent that one year after transplantation the telomere length in recipient cells was similar to the telomere length in donor-derived cells. Therefore, our data indicate telomere length homeostasis after peripheral blood stem cell transplantation, implying no loss of replicative capacity of the stem cells. Our data indicate that fast expansion is accompanied by a reduction of telomere length and that telomere length homeostasis is achieved by de novo generation of hematopoietic cells from stem cells without transplantation-related telomere loss.
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