Accelerated telomere shortening in young recipients of allogeneic bone-marrow transplants

Lancet
R F WynnN G Testa

Abstract

The establishment of donor-derived haemopoiesis in the recipients of allogeneic bone-marrow transplants (BMT) involves extensive proliferation of haemopoietic stem cells. The biological consequences of this replicative stress are ill defined, but any "ageing" effect would carry the risk of an increased frequency of clonal disorders during later life. We compared blood-cell mean telomere lengths in donor/recipient pairs. Mean telomere length was calculated by in-gel hybridisation to leucocyte DNA from 56 normal individuals aged 0-96 years, and from 14 consecutive BMT recipients (aged 2-14 years) plus their respective donors (aged 2-46 years). Engraftment was confirmed by variable numbers of tandem repeats (VNTR) or gender analysis. On average, blood-cell telomeres of transplant recipients were 0.4 kb (95% CI -0.2 to -0.6) shorter than those of their respective donors. This degree of telomere loss is equivalent to a median of 15 years' (range 0-40) ageing in the healthy controls. The kinetics of haemopoietic engraftment impose replicative stress on the haemopoietic stem cells, resulting in a pronounced ageing effect, which may be sufficient to accelerate the onset of clonal haemopoietic disorders usually associated with later lif...Continue Reading

References

Aug 30, 1990·Nature·N D HastieR C Allshire
Sep 21, 1989·The New England Journal of Medicine·R P WitherspoonR Storb
Jan 1, 1989·Proceedings of the National Academy of Sciences of the United States of America·E BoerwinkleL Chan
Feb 1, 1987·Cancer Nursing·A C Yeomans
Nov 21, 1995·Proceedings of the National Academy of Sciences of the United States of America·E Chang, C B Harley
Jan 3, 1995·Proceedings of the National Academy of Sciences of the United States of America·P A KrukV A Bohr
Oct 11, 1994·Proceedings of the National Academy of Sciences of the United States of America·H VaziriP M Lansdorp
Jul 1, 1996·Nature Genetics·J A MetcalfeA M Taylor
Mar 27, 1997·The New England Journal of Medicine·R E CurtisJ D Boice
Jul 31, 1997·The New England Journal of Medicine·R M Pearl

❮ Previous
Next ❯

Citations

Oct 26, 2007·Cell and Tissue Research·Stefan Zimmermann, Uwe M Martens
Apr 1, 2002·Journal of the American Aging Association·Gerald de Haan, Gary Van Zant
Jan 22, 2004·Archives of Medical Research·Matthew J Greenwood, Peter M Lansdorp
Mar 11, 2004·The International Journal of Biochemistry & Cell Biology·Ilaria Bellantuono
Jun 12, 2003·Experimental Cell Research·Giordano BianchiRodolfo Quarto
Dec 20, 2000·Transplantation Proceedings·S GotoC L Chen
Feb 13, 2001·Mechanisms of Ageing and Development·A N AkbarM Salmon
Feb 19, 2002·Mechanisms of Ageing and Development·Mo K KangNo-Hee Park
Sep 15, 2000·Clinics in Perinatology·C Dame, S E Juul
Sep 27, 2003·Lancet·Judy M Y Wong, Kathleen Collins
Aug 7, 2003·Experimental Hematology·Gary Van Zant, Ying Liang
Jun 11, 1999·Experimental Gerontology·A Globerson
Jan 23, 1999·Current Opinion in Cell Biology·C T Jordan, G Van Zant
Feb 14, 2002·Critical Reviews in Oncology/hematology·Meaghan P GrangerJerry W Shay
Jun 23, 1999·Molecular Medicine Today·D R Jones
Nov 13, 2008·Cytotechnology·Andrew D ClarkTessa L Holyoake
Jul 19, 2013·Molecular Therapy : the Journal of the American Society of Gene Therapy·Stephanie E SellersCynthia E Dunbar
Dec 19, 1998·British Journal of Haematology·R F WynnN G Testa
Nov 11, 1999·British Journal of Haematology·F LeteurtreE Gluckman
Apr 12, 2001·British Journal of Haematology·J J LeeH J Kim
Dec 17, 2009·The New England Journal of Medicine·Rodrigo T Calado, Neal S Young
Feb 7, 2001·Transplantation·S GotoC L Chen
Aug 15, 1998·Vox Sanguinis·P M Lansdorp
Jan 7, 2009·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Sujata ChakrabortyRavi Bhatia
May 15, 2010·Future Oncology·Michelle F MaritzKaren L MacKenzie

❮ Previous
Next ❯

Related Concepts

Related Feeds

Allogenic & Autologous Therapies

Allogenic therapies are generated in large batches from unrelated donor tissues such as bone marrow. In contrast, autologous therapies are manufactures as a single lot from the patient being treated. Here is the latest research on allogenic and autologous therapies.