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

2.50
Hdl Handle:
http://hdl.handle.net/10541/92345
Title:
Accelerated telomere shortening in young recipients of allogeneic bone-marrow transplants.
Authors:
Wynn, Robert F; Cross, Michael A; Hatton, C; Will, A M; Lashford, Linda S; Dexter, T Michael; Testa, Nydia G
Abstract:
BACKGROUND: 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. METHODS: 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. FINDINGS: 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. INTERPRETATION: 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 life. Monitoring of haemopoietic status in BMT recipients as time since BMT increases will be important. Assessment of transplant protocols under development in terms of their effects on telomere shortening is also indicated.
Affiliation:
Cancer Research Campaign Department of Experimental Haematology, Paterson Institute for Cancer Research, Christie Hospital NHS Trust, Manchester, UK.
Citation:
Accelerated telomere shortening in young recipients of allogeneic bone-marrow transplants. 1998, 351 (9097):178-81 Lancet
Journal:
Lancet
Issue Date:
17-Jan-1998
URI:
http://hdl.handle.net/10541/92345
DOI:
10.1016/S0140-6736(97)08256-1
PubMed ID:
9449873
Type:
Article
Language:
en
ISSN:
0140-6736
Appears in Collections:
All Christie Publications ; All Paterson Institute for Cancer Research

Full metadata record

DC FieldValue Language
dc.contributor.authorWynn, Robert Fen
dc.contributor.authorCross, Michael Aen
dc.contributor.authorHatton, Cen
dc.contributor.authorWill, A Men
dc.contributor.authorLashford, Linda Sen
dc.contributor.authorDexter, T Michaelen
dc.contributor.authorTesta, Nydia Gen
dc.date.accessioned2010-02-17T12:02:51Z-
dc.date.available2010-02-17T12:02:51Z-
dc.date.issued1998-01-17-
dc.identifier.citationAccelerated telomere shortening in young recipients of allogeneic bone-marrow transplants. 1998, 351 (9097):178-81 Lanceten
dc.identifier.issn0140-6736-
dc.identifier.pmid9449873-
dc.identifier.doi10.1016/S0140-6736(97)08256-1-
dc.identifier.urihttp://hdl.handle.net/10541/92345-
dc.description.abstractBACKGROUND: 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. METHODS: 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. FINDINGS: 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. INTERPRETATION: 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 life. Monitoring of haemopoietic status in BMT recipients as time since BMT increases will be important. Assessment of transplant protocols under development in terms of their effects on telomere shortening is also indicated.en
dc.language.isoenen
dc.subjectHaematopoiesisen
dc.subjectHaematopoietic Stem Cellsen
dc.subject.meshAdolescent-
dc.subject.meshBone Marrow Transplantation-
dc.subject.meshCell Aging-
dc.subject.meshChild-
dc.subject.meshChild, Preschool-
dc.subject.meshFemale-
dc.subject.meshHematopoiesis-
dc.subject.meshHematopoietic Stem Cells-
dc.subject.meshHumans-
dc.subject.meshMale-
dc.subject.meshTelomere-
dc.subject.meshTime Factors-
dc.subject.meshTransplantation, Homologous-
dc.titleAccelerated telomere shortening in young recipients of allogeneic bone-marrow transplants.en
dc.typeArticleen
dc.contributor.departmentCancer Research Campaign Department of Experimental Haematology, Paterson Institute for Cancer Research, Christie Hospital NHS Trust, Manchester, UK.en
dc.identifier.journalLanceten

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