title: High levels of global DNA methylation are an independent adverse prognostic factor in a series of 90 patients with de novo myelodysplastic syndrome.
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.
authors.affiliation: Hematopathology Unit, Department of Pathology, Hospital Clínic, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), University of Barcelona, Barcelona, Spain. Electronic address: xcalvo@clinic.ub.es.
authors.forename: Xavier
authors.initials: X
authors.lastname: Calvo
authors.affiliation: Hematology Department, Hospital Clínic, IDIBAPS, University of Barcelona, Barcelona, Spain; Josep Carreras Leukaemia Research Institute, Barcelona, Spain.
authors.forename: Meritxell
authors.initials: M
authors.lastname: Nomdedeu
authors.affiliation: Molecular Oncology and Embryology Laboratory, Human Anatomy Unit, School of Medicine, University of Barcelona, IDIBAPS, Barcelona, Spain.
authors.forename: Alfons
authors.initials: A
authors.lastname: Navarro
authors.affiliation: Molecular Oncology and Embryology Laboratory, Human Anatomy Unit, School of Medicine, University of Barcelona, IDIBAPS, Barcelona, Spain.
authors.forename: Rut
authors.initials: R
authors.lastname: Tejero
authors.affiliation: Hematopathology Unit, Department of Pathology, Hospital Clínic, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), University of Barcelona, Barcelona, Spain.
authors.forename: Dolors
authors.initials: D
authors.lastname: Costa
authors.affiliation: Hematopathology Unit, Department of Pathology, Hospital Clínic, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), University of Barcelona, Barcelona, Spain.
authors.forename: Concha
authors.initials: C
authors.lastname: Muñoz
authors.affiliation: Department of Hemotherapy and Hemostasis, Hospital Clínic, IDIBAPS, University of Barcelona, Barcelona, Spain.
authors.forename: Arturo
authors.initials: A
authors.lastname: Pereira
authors.affiliation: Hematology Department, Hospital Clínic, IDIBAPS, University of Barcelona, Barcelona, Spain.
authors.forename: Oscar
authors.initials: O
authors.lastname: Peña
authors.affiliation: Josep Carreras Leukaemia Research Institute, Barcelona, Spain.
authors.forename: Ruth M
authors.initials: RM
authors.lastname: Risueño
authors.affiliation: Molecular Oncology and Embryology Laboratory, Human Anatomy Unit, School of Medicine, University of Barcelona, IDIBAPS, Barcelona, Spain.
authors.forename: Mariano
authors.initials: M
authors.lastname: Monzó
authors.affiliation: Hematology Department, Hospital Clínic, IDIBAPS, University of Barcelona, Barcelona, Spain; Josep Carreras Leukaemia Research Institute, Barcelona, Spain.
authors.forename: Jordi
authors.initials: J
authors.lastname: Esteve
authors.affiliation: Hematology Department, Hospital Clínic, IDIBAPS, University of Barcelona, Barcelona, Spain. Electronic address: nomdedeu@clinic.ub.es.
authors.forename: Benet
authors.initials: B
authors.lastname: Nomdedeu
mesh_terms: D044503:5-Methylcytosine / Q000032:analysis / Q000031:analogs & derivatives; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001853:Bone Marrow / Q000737:chemistry / Q000473:pathology; D003596:Cytosine / Q000031:analogs & derivatives / Q000032:analysis; D004247:DNA / Q000032:analysis; D019175:DNA Methylation; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000235:genetics* / Q000401:mortality* / Q000473:pathology; D011379:Prognosis; D016019:Survival Analysis
chemical_list: C011865:5-hydroxymethylcytosine; D044503:5-Methylcytosine; D003596:Cytosine; D004247:DNA
keywords: 5-hmC; 5-mC; Hydroxymethylation; Methylation; Myelodysplastic syndromes; Prognosis