Cell-free DNA fragmentomics and epigenomic profiling in hematologic malignancies: current evidence, translational limitations, and future directions

Abstract

Highlights • Evidence mapping separates direct plasma studies from indirect support.• Fragmentomic and epigenomic signals may complement mutation testing.• Lineage-associated methylation does not establish malignant fraction.• Multimodal profiling often requires separate assays and integration.• Most applications still require independent prospective validation.