The Chronic Lymphocytic Leukemia Epigenome: A Powerful and Stable Framework for Understanding Biological and Clinical Heterogeneity.

This review explores how epigenetic information, and in particular DNA methylation-based "epitypes," enhances our understanding of chronic lymphocytic leukemia (CLL) biology and prognosis. Epitypes correlate with B-cell maturation stages and outperform traditional biomarkers like immunoglobulin heavy chain variable region mutation status in predicting outcomes. The stability and specificity of CLL epigenetic patterns offer insights into disease history, risk stratification, and treatment response, even amid evolving therapeutic landscape. Emerging epigenetic signatures, including proliferative indices, further refine patient classification and outcome prediction, underscoring the potential clinical utility of integrating epigenetic data in CLL management.