Methylation markers identify high risk patients in IGHV mutated chronic lymphocytic leukemia
Volume 6, Issue 3
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Pages 300 - 306http://dx.doi.org/10.4161/epi.6.3.14038
Authors: Laura Irving, Tryfonia Mainou-Fowler, Anton Parker, Rachel E. Ibbotson, David G. Oscier and Gordon Strathdee View affiliations
Chronic lymphocytic leukemia (CLL) exhibits a very variable clinical course. Altered DNA methylation of genes has shown promise as a source of novel prognostic makers in a number of cancers. Here we have studied the potential utility of a panel of methylation markers (CD38, HOXA4 and BTG4) in 118 CLL patients. Each of the three loci assessed exhibited frequent methylation, as determined by COBRA analysis, and individually correlated with either good (CD38, BTG4 methylation) or poor (HOXA4 methylation) prognosis. Using a combined approach to produce an overall methylation score, we found that methylation score was significantly associated with time to first treatment in CLL patients. Multivariate Cox regression analysis revealed that methylation score was the strongest predictor of time to first treatment, and was independent of IGHV gene mutational status and CD38 expression. This study provides proof of principle that a panel of methylation markers can be used for additional risk stratification of CLL patients.
Received: August 24, 2010; Accepted: October 28, 2010