High levels of global DNA methylation are an independent adverse prognostic factor in a series of 90 patients with de novo myelodysplastic syndrome

• Published in: Leukemia research Vol. 38; no. 8; pp. 874 - 881
• Main Authors: Calvo, Xavier, Nomdedeu, Meritxell, Navarro, Alfons, Tejero, Rut, Costa, Dolors, Muñoz, Concha, Pereira, Arturo, Peña, Oscar, Risueño, Ruth M, Monzó, Mariano, Esteve, Jordi, Nomdedeu, Benet
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01.08.2014
• Subjects: 5-hmC; 5-mC; 5-Methylcytosine - analysis; Adult; Aged; Aged, 80 and over; Bone Marrow - chemistry; Bone Marrow - pathology; Cytosine - analogs & derivatives; Cytosine - analysis; DNA - analysis; DNA Methylation; Female; Hematology, Oncology and Palliative Medicine; Humans; Hydroxymethylation; Male; Methylation; Middle Aged; Myelodysplastic syndromes; Myelodysplastic Syndromes - genetics; Myelodysplastic Syndromes - mortality; Myelodysplastic Syndromes - pathology; Prognosis; Survival Analysis; Hydroxymethylation; Prognosis; Methylation; 5-mC; 5-hmC; Myelodysplastic syndromes
• ISSN: 0145-2126; 1873-5835
• DOI: 10.1016/j.leukres.2014.04.015

Abstract The prognostic impact of global DNA methylation and hydroxymethylation was assessed in 90 patients with de novo myelodysplastic syndrome (MDS). DNA was isolated from bone marrow samples obtained at diagnosis and global methylation and hydroxymethylation were determined by ELISA. Patients with a percentage of methylated DNA above 2.73% had a shorter overall survival than those with lower levels ( P = 0.018) and presented a negative trend in terms of leukemia-free survival ( P = 0.084), that was statistically significant after censoring 9 patients that received disease-modifying treatments both in univariate and multivariate analyses. Similarly, the low-risk MDS patients defined by the IPSS, WPSS and IPSS-R with 5-mC percentage in total DNA above 2.73% had a shorter overall survival ( P = 0.032; P = 0.023; P = 0.031). No cut-off value for the 5-hydroxymethylcytosine percentage with statistical significance for overall or leukemia-free survival was obtained. This study suggests that global DNA methylation predicts overall survival in myelodysplastic syndromes.