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Allografting

A constitutional variant in the transcription factor EP300 strongly influences the clinical outcome of patients submitted to allo-SCT

Bone Marrow Transplantation volume 47, pages 1206–1211 (2012)Cite this article

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Abstract

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.

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Acknowledgements

This work has been supported by project PI08/1137 from ISCIII (Instituto de Salud Carlos III), project RD06/0020/0012 from RTICC (Red Temática de Investigación Cooperativa en Cáncer) and project PI0079 from Consejería de Salud, Junta de Andalucía. We thank Bernat Gel for all the statistical advice.

Author contributions: AU and BM designed the study; AU obtained funding; JF, IE, MS, MR, FFA, CM, FM and RC obtained clinical data; BM, IA and AB obtained genetic data; BM performed the statistical analysis; AU and BM drafted the manuscript.

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Authors and Affiliations

  1. Department of Hematology, Hospital Clinic, Universidad Barcelona, IDIBAPS, Josep Carreras Leukemia Research Institute, Barcelona, Spain

    B Martín-Antonio, M Suarez-Lledo, F Fernández-Avilés, C Martínez, M Rovira & Á Urbano-Ispizua

  2. Department of Hematology,Hospital Universitario Virgen del Rocío, Universidad de Sevilla. Instituto de Biomedicina de Sevilla (IBIS), Seville, Spain

    I Álvarez-Laderas, R Cardesa, F Márquez-Malaver, A Baez, M Carmona, J Falantes & I Espigado

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  1. B Martín-Antonio
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Correspondence to B Martín-Antonio.

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This work has been supported by project PI08/1137 from ISCIII (Instituto de Salud Carlos III), project RD06/0020/0012 from RTICC (Red Temática de Investigación Cooperativa en Cáncer) and project PI0079 from Consejería de Salud, Junta de Andalucía.

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Martín-Antonio, B., Álvarez-Laderas, I., Cardesa, R. et al. A constitutional variant in the transcription factor EP300 strongly influences the clinical outcome of patients submitted to allo-SCT. Bone Marrow Transplant 47, 1206–1211 (2012). https://doi.org/10.1038/bmt.2011.253

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