Mutation-specific impairment of TET2 and DNMT3A enzymatic activity predicts clonal hematopoiesis disease risk - PubMed
3 hours ago
- #Clonal Hematopoiesis
- #Risk Prediction
- #DNA Methylation
- The study analyzed over 1 million individuals to show that enzymatically disruptive mutations in TET2 and DNMT3A, particularly TET2 loss-of-function and DNMT3A R882, drive most clonal hematopoiesis (CHIP) disease risk.
- Methylation-based activity scores for TET2 and DNMT3A were developed as biomarkers to quantify enzymatic dysfunction, capturing functional heterogeneity across mutation subtypes.
- These scores predict disease risk comparably to existing clinical models and, when integrated, significantly improve prediction of cytopenia, myeloid neoplasm, and cardiovascular events.