title: DNA methylation dynamics in blood after hematopoietic cell transplant.
abstract: 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.
authors: Cancer Epigenetics Laboratory, Instituto Universitario de Oncología del Principado de Asturias, HUCA, Universidad de Oviedo, Oviedo, Spain.
authors: Ramon M
authors: RM
authors: Rodriguez
authors: Beatriz
authors: B
authors: Suarez-Alvarez
authors: Rubén
authors: R
authors: Salvanés
authors: Manuel
authors: M
authors: Muro
authors: Pablo
authors: P
authors: Martínez-Camblor
authors: Enrique
authors: E
authors: Colado
authors: Miguel Alcoceba
authors: MA
authors: Sánchez
authors: Marcos González
authors: MG
authors: Díaz
authors: Agustin F
authors: AF
authors: Fernandez
authors: Mario F
authors: MF
authors: Fraga
authors: Carlos
authors: C
authors: Lopez-Larrea
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D019175:DNA Methylation / Q000235:genetics*; D053222:Fas Ligand Protein / Q000097:blood; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007371:Interferon-gamma / Q000097:blood; D016753:Interleukin-10 / Q000097:blood; D008297:Male; D008875:Middle Aged; D054353:Perforin; D052899:Pore Forming Cytotoxic Proteins / Q000097:blood; D055815:Young Adult
chemical_list: C505661:FASLG protein, human; D053222:Fas Ligand Protein; C510468:PRF1 protein, human; D052899:Pore Forming Cytotoxic Proteins; D054353:Perforin; D016753:Interleukin-10; D007371:Interferon-gamma