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Prepublished online as a Blood First Edition Paper on August 22, 2002; DOI 10.1182/blood-2002-06-1832.
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Blood, 1 January 2003, Vol. 101, No. 1, pp. 358-362
TRANSPLANTATION
Homeostasis of telomere length rather than
telomere shortening after allogeneic peripheral blood stem cell
transplantation
Helene Roelofs,
Elmar S. D. de Pauw,
Aeilko H. Zwinderman,
Sonja M. Opdam,
Roel Willemze,
Hans J. Tanke, and
Willem E. Fibbe
From the Departments of Hematology, Medical Statistics,
and Molecular Cell Biology, Leiden University Medical Center, The
Netherlands.
Hematopoietic reconstitution after stem cell transplantation
requires excessive replicative activity because of the limited number
of stem cells that are used for transplantation. Telomere shortening
has been detected in hematopoietic cells after bone marrow
transplantation. This has been thought to result from excessive replication of the stem cells, with putative concomitant reduction of
their replicative potential. 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 hematologic recovery and telomere length
dynamics in the immediate reconstitution period after allogeneic
T-cell-depleted blood stem cell transplantation. We
analyzed hematologic 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 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 1 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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