Por favor, use este identificador para citar o enlazar este Item:http://hdl.handle.net/20.500.12105/19114
Título
Telomere shortening in enterocytes of patients with uncontrolled acute intestinal graft-versus-host disease.
Autor(es)
Fecha de publicación
2015-11-26
Cita
Blood . 2015 ;126(22):2518-21.
Idioma
Inglés
Tipo de documento
journal article
Resumen
Acute intestinal graft-versus-host disease (aGVHD) refractory to immunosuppressive treatment is a serious complication after allogenic hematopoietic stem cell transplantation (HSCT). The underlying mechanisms of refractory aGVHD of the gut are not fully understood. Although telomere length (TL) reflects the replicative history of a cell, critically short telomeres have been associated with replicative exhaustion and tissue failure. In this study, we demonstrate that enterocytes of patients with refractory intestinal aGVHD show significantly increased proliferation, which translates into significant and critical telomere attrition following HSCT as compared with unaffected patients undergoing HSCT. Calculated telomere loss in aGVHD patients is 190 bp/wk, thereby massively exceeding physiological steady-state TL shortening rates such as in lymphocytes (∼50 bp/y). Our data support the hypothesis that increased compensatory proliferation following continued tissue damage can result in massive telomere loss in enterocytes of aGVHD patients. The present study introduces aGVHD-triggered increased cellular turnover and telomere loss with subsequent replicative exhaustion as a mechanism for refractory gut GVHD that is compatible with the long-term clinical aspect of the disease and provides a basis for stem cell protective therapies in the treatment of aGVHD.
MESH
Cell Proliferation | Hematopoietic Stem Cell Transplantation | Telomere Shortening | Acute Disease | Allografts | Enterocytes | Female | Graft vs Host Disease | Humans | Intestinal Diseases | Male | Retrospective Studies
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