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A constitutional variant in the transcription factor EP300 strongly influences the clinical outcome of patients submitted to allo-SCT.
MedLine Citation:
PMID:  22231458     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
An adequate response of the innate immune system after allo-SCT is crucial for the clinical outcome of patients submitted to this procedure. EP300 is one of the key genes of the innate immune system (IIS). We evaluated the influence of gene variant A>G rs20551 in EP300 in donor and/or recipient on clinical results after HLA-identical sibling allo-SCT. Patients with AA gene variant had a lower relapse incidence (31 vs 48%, P=0.025; odds ratio (OR)=1.6, P=0.05), attained better disease-free survival (AA: 53% vs AG+GG: 24%, P=0.001; OR=1.8, P=0.01), and better OS (AA: 53% vs AG+GG: 34%, P=0.001; OR=1.9, P=0.007). This beneficial association was more evident when AA gene variant was present in both donor and patient. In healthy individuals, AA gene variant was associated with lower IL2 production after a mitogenic stimuli, higher CD4+ cell response after CMV infection, and higher expression of innate immune genes (IRF-3 and MIF), cell cycle genes (AURKB, CCNA2 and CCNB1), lymphocyte survival genes (NFAT5 and SLC38A2), and with a lower expression of P53 compared with recessive GG gene variant. These findings suggest a beneficial effect of the AA gene variant in rs20551 on clinical outcome after allo-SCT.Bone Marrow Transplantation advance online publication, 9 January 2012; doi:10.1038/bmt.2011.253.
Authors:
B Martín-Antonio; I Alvarez-Laderas; R Cardesa; F Márquez-Malaver; A Baez; M Carmona; J Falantes; M Suarez-Lledo; F Fernández-Avilés; C Martínez; M Rovira; I Espigado; A Urbano-Ispizua
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-1-09
Journal Detail:
Title:  Bone marrow transplantation     Volume:  -     ISSN:  1476-5365     ISO Abbreviation:  -     Publication Date:  2012 Jan 
Date Detail:
Created Date:  2012-1-10     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8702459     Medline TA:  Bone Marrow Transplant     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
Department of Hematology, Hospital Clinic, Universidad Barcelona, IDIBAPS, Josep Carreras Leukemia Research Institute, Barcelona, Spain.
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