Distinct patterns of global promoter methylation in early stage chronic lymphocytic leukemia

Domenica Ronchetti, Giacomo Tuana, Andrea Rinaldi, Luca Agnelli, Giovanna Cutrona, Laura Mosca, Sonia Fabris, Serena Matis, Monica Colombo, Massimo Gentile, Anna Grazia Recchia, Ivo Kwee, Francesco Bertoni, Fortunato Morabito, Manlio Ferrarini, Antonino Neri

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Pages (from-to)264-273
Number of pages10
JournalGenes Chromosomes and Cancer
Volume53
Issue number3
DOIs
Publication statusPublished - Mar 2014

ASJC Scopus subject areas

  • Cancer Research
  • Genetics

Fingerprint

Dive into the research topics of 'Distinct patterns of global promoter methylation in early stage chronic lymphocytic leukemia'. Together they form a unique fingerprint.

Cite this