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Updated: Oct 5, 2025
Comprehensive DNA Methylation Analysis Using a Methyl-CpG-binding Domain Capture-based Method in Chronic Lymphocytic Leukemia Patients
Published on: June 16, 2017
Evaluation of a Prognostic Epigenetic Classification System in Chronic Lymphocytic Leukemia Patients
Christina Grimm1,2, Carmen Diana Herling3,4,5, Anastasia Komnidi1,2
1Institute for Translational Epigenetics, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany.
Background:
Methylation at 5 CpG sites was previously shown to classify chronic lymphocytic leukemia (CLL) into 3 prognostic subgroups. Here, we aimed to validate the marker set in an additional cohort and to evaluate its clinical utility for CLL patient stratification.
Methods:
We evaluated this epigenetic marker set in 79 German patients using bisulfite treatment followed by pyrosequencing and classification using a support vector machine-learning tool.
Results:
The n-CLL, i-CLL, and m-CLL classification was detected in 28 (35%), 10 (13%), and 41 (51%) patients, respectively. Epigenetic grouping was associated with IGHV mutational status (P = 2 × 10-12), isolated del13q (P = 9 × 10-6), del17p (P = .015), complex karyotype (P = .005), VH-usage, and clinical outcome as time to first treatment (P = 1.4 × 10-12) and overall survival (P = .003). Multivariate Cox regression analysis identified n-CLL as a factor for earlier treatment hazard ratio (HR), 6.3 (95% confidence interval [CI] 2.4-16.4; P = .0002) compared to IGHV mutational status (HR 4.6, 95% CI 1.9-11.3, P = .0008). In addition, when comparing the prognostic value of the epigenetic classification system with the IGHV classification, epigenetic grouping performed better compared to IGHV mutational status using Kaplan-Meier estimation and allowed the identification of a third, intermediate (i-CLL) group. Thus, our study confirmed the prognostic value of the epigenetic marker set for patient stratification in routine clinical diagnostics.
