دورية أكاديمية
Polymorphism in TGFB1 is associated with worse non-relapse mortality and overall survival after stem cell transplantation with unrelated donors
| العنوان: | Polymorphism in TGFB1 is associated with worse non-relapse mortality and overall survival after stem cell transplantation with unrelated donors |
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| المؤلفون: | Esteban Arrieta-Bolaños, Neema P. Mayor, Steven G.E. Marsh, J. Alejandro Madrigal, Jane F. Apperley, Keiren Kirkland, Stephen Mackinnon, David I. Marks, Grant McQuaker, Julia Perry, Michael N. Potter, Nigel H. Russell, Kirsty Thomson, Bronwen E. Shaw |
| المصدر: | Haematologica, Vol 101, Iss 3 (2016) |
| بيانات النشر: | Ferrata Storti Foundation, 2016. |
| سنة النشر: | 2016 |
| المجموعة: | LCC:Diseases of the blood and blood-forming organs |
| مصطلحات موضوعية: | Diseases of the blood and blood-forming organs, RC633-647.5 |
| الوصف: | Transforming growth factor β-1, encoded by the TGFB1 gene, is a cytokine that plays a central role in many physiological and pathogenic processes. We have sequenced TGFB1 regulatory region and assigned allelic genotypes in a large cohort of hematopoietic stem cell transplantation patients and donors. In this study, we analyzed 522 unrelated donor-patient pairs and examined the combined effect of all the common polymorphisms in this genomic region. In univariate analysis, we found that patients carrying a specific allele, ‘p001’, showed significantly reduced overall survival (5-year overall survival 30.7% for p001/p001 patients vs. 41.6% others; P=0.032) and increased non-relapse mortality (1-year non-relapse mortality: 39.0% vs. 25.4%; P=0.039) after transplantation. In multivariate analysis, the presence of a p001/p001 genotype in patients was confirmed as an independent factor for reduced overall survival [hazard ratio=1.53 (1.04–2.24); P=0.031], and increased non-relapse mortality [hazard ratio=1.73 (1.06–2.83); P=0.030]. In functional experiments we found a trend towards a higher percentage of surface transforming growth factor β-1-positive regulatory T cells after activation when the cells had a p001 allele (P=0.07). Higher or lower production of transforming growth factor β-1 in the inflammatory context of hematopoietic stem cell transplantation may influence the development of complications in these patients. Findings indicate that TGFB1 genotype could potentially be of use as a prognostic factor in hematopoietic stem cell transplantation risk assessment algorithms. |
| نوع الوثيقة: | article |
| وصف الملف: | electronic resource |
| اللغة: | English |
| تدمد: | 0390-6078 1592-8721 |
| العلاقة: | https://haematologica.org/article/view/7657Test; https://doaj.org/toc/0390-6078Test; https://doaj.org/toc/1592-8721Test |
| DOI: | 10.3324/haematol.2015.134999 |
| الوصول الحر: | https://doaj.org/article/10211a0729b0476e918d0ed826e11fb2Test |
| رقم الانضمام: | edsdoj.10211a0729b0476e918d0ed826e11fb2 |
| قاعدة البيانات: | Directory of Open Access Journals |
Full Text Finder | تدمد: | 03906078 15928721 |
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| DOI: | 10.3324/haematol.2015.134999 |