Open AccessDNA Methylation Dynamics in Blood after Hematopoietic Cell Transplant
Author(s) -
Ramón María Alvargonzález Rodríguez,
Beatriz Suárez-Álvarez,
Rubén Salvanés,
Manuel Muro,
Pablo Martínez–Camblor,
Enrique Colado,
Miguel Alcoceba,
Marcos González Díaz,
Agustín F. Fernández,
Mario F. Fraga,
Carlos LópezLarrea
Publication year - 2013
Publication title -
plos one
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.99
H-Index - 332
ISSN - 1932-6203
DOI - 10.1371/journal.pone.0056931
Subject(s) - dna methylation , epigenetics , methylation , biology , immunology , transplantation , cancer research , medicine , genetics , dna , gene , gene expression
Epigenetic deregulation is considered a common hallmark of cancer. Nevertheless, recent publications have demonstrated its association with a large array of human diseases. Here, we explore the DNA methylation dynamics in blood samples during hematopoietic cell transplant and how they are affected by pathophysiological events during transplant evolution. We analyzed global DNA methylation in a cohort of 47 patients with allogenic transplant up to 12 months post-transplant. Recipients stably maintained the donor’s global methylation levels after transplant. Nonetheless, global methylation is affected by chimerism status. Methylation analysis of promoters revealed that methylation in more than 200 genes is altered 1 month post-transplant when compared with non-pathological methylation levels in the donor. This number decreased by 6 months post-transplant. Finally, we analyzed methylation in IFN-γ, FASL, IL-10, and PRF1 and found association with the severity of the acute graft-versus-host disease. Our results provide strong evidence that methylation changes in blood are linked to underlying physiological events and demonstrate that DNA methylation analysis is a viable strategy for the study of transplantation and for development of biomarkers.