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Telomeres, X-Inactivation Ratios, and Hematopoietic Stem Cell Transplantation in Humans: A Review

Division of Hematology/Oncology, The Hospital for Sick Children, University of Toronto, Ontario, Canada

Key Words. Hematopoietic stem cell • Hematopoietic stem cell transplantation • Telomere • X-inactivation ratio • Hematopoietic reconstitution

Ian Thornley, MBBS, MRCP(UK), Division of Hematology/Oncology, The Hospital for Sick Children, 555 University Avenue, Toronto, Ontario M5G 1X8, Canada. Telephone: 416-813-5977; Fax: 416-813-5327; e-mail: ihthornley{at}hotmail.com

The marrow repopulating hematopoietic stem cells (HSCs) in an auto- or allograft represent a small fraction of the normal complement of HSCs, yet are required to reconstitute hematopoiesis and sustain it for the lifetime of the recipient. Such a burden imposes a "replicative stress" upon hematopoietic stem/progenitor cells. The finding of accelerated telomere shortening in hematopoietic stem cell transplant (HSCT) recipients raised the specter of accelerated hematopoietic aging. Here, we review the HSCT telomere literature and other studies of surrogate markers of HSC behavior conducted in human HSCT recipients. We present a paradigm for posttransplant hematopoietic reconstitution and speculate on the fate of HSCs in the human transplant setting.

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