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dc.contributor.authorWynn, Robert F
dc.contributor.authorCross, Michael A
dc.contributor.authorHatton, C
dc.contributor.authorWill, A M
dc.contributor.authorLashford, Linda S
dc.contributor.authorDexter, T Michael
dc.contributor.authorTesta, Nydia G
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.
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
html.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.


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