Hummel, Sebastian and Ferreira, Monica S. Ventura and Heudobler, Daniel and Huber, Elisabeth and Fahrenkamp, Dirk and Gremse, Felix and Schmid, Karin and Mueller-Newen, Gerhard and Ziegler, Patrick and Jost, Edgar and Blasco, Maria A. and Bruemmendorf, Tim H. and Holler, Ernst and Beier, Fabian (2015) Telomere shortening in enterocytes of patients with uncontrolled acute intestinal graft-versus-host disease. BLOOD, 126 (22). pp. 2518-2521. ISSN 0006-4971, 1528-0020
Full text not available from this repository. (Request a copy)Abstract
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 (similar to 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.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | STEM-CELLS; DYSKERATOSIS-CONGENITA; LENGTH DYNAMICS; TRF1 KNOCKOUT; MARKER; |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Innere Medizin III (Hämatologie und Internistische Onkologie) |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 06 May 2019 08:12 |
| Last Modified: | 06 May 2019 08:12 |
| URI: | https://pred.uni-regensburg.de/id/eprint/4439 |
Actions (login required)
 |
View Item |
