title: Distinct patterns of global promoter methylation in early stage chronic lymphocytic leukemia.
abstract: Genomic and epigenomic studies of chronic lymphocytic leukemia (CLL) are reshaping our understanding of the disease and have provided new perspectives for a more individualized diagnosis and new potential therapeutic targets. In this study, the global promoter methylation profile was determined in highly purified B-cells from 37 (Binet stage A) CLL patients, using high-resolution methylation microarrays (27,578 CpG). Overall, the methylation pattern correlated with the major biological (ZAP-70 and CD38), and molecular (IGHV mutation) markers, distinguishing CLL cases according to IGHV mutational status. Cell adhesion molecules were enriched in the signature of unmutated (UM) versus mutated (M-) CLL. Moreover, in M-CLL CpG hyper-methylation in three genes, including SPG20, was significantly anti-correlated with the corresponding gene expression level. Finally, the correlation between the methylation pattern and clinical parameters was investigated. Notably, out of 42 methyl-probes that were significantly associated with progression free survival (PFS), hyper-methylation of SPG20 was also positively associated with PFS. These data support the notion that epigenetic changes have clinical impact in CLL and may contribute to the identification of novel candidate disease-associated genes potentially useful to predict the clinical outcome of early stage CLL patients.
authors.affiliation: Department of Clinical Sciences and Community Health, University of Milano, Milano, Italy.
authors.forename: Domenica
authors.initials: D
authors.lastname: Ronchetti
authors.forename: Giacomo
authors.initials: G
authors.lastname: Tuana
authors.forename: Andrea
authors.initials: A
authors.lastname: Rinaldi
authors.forename: Luca
authors.initials: L
authors.lastname: Agnelli
authors.forename: Giovanna
authors.initials: G
authors.lastname: Cutrona
authors.forename: Laura
authors.initials: L
authors.lastname: Mosca
authors.forename: Sonia
authors.initials: S
authors.lastname: Fabris
authors.forename: Serena
authors.initials: S
authors.lastname: Matis
authors.forename: Monica
authors.initials: M
authors.lastname: Colombo
authors.forename: Massimo
authors.initials: M
authors.lastname: Gentile
authors.forename: Anna Grazia
authors.initials: AG
authors.lastname: Recchia
authors.forename: Ivo
authors.initials: I
authors.lastname: Kwee
authors.forename: Francesco
authors.initials: F
authors.lastname: Bertoni
authors.forename: Fortunato
authors.initials: F
authors.lastname: Morabito
authors.forename: Manlio
authors.initials: M
authors.lastname: Ferrarini
authors.forename: Antonino
authors.initials: A
authors.lastname: Neri
mesh_terms: D000368:Aged; D018899:CpG Islands; D005260:Female; D015870:Gene Expression; D020869:Gene Expression Profiling; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000175:diagnosis / Q000235:genetics* / Q000378:metabolism; D008297:Male; D008745:Methylation; D015337:Multicenter Studies as Topic; D011379:Prognosis; D011401:Promoter Regions, Genetic; D011446:Prospective Studies; D059467:Transcriptome