Randomized trial investigates DNA methylation's impact on clinical outcomes in pediatric AML, suggesting potential for better risk management.
Key Points
This research aims to explore the relationship between DNA methylation patterns and clinical outcomes in pediatric acute myeloid leukemia (AML).
Analyzed DNA methylation profiles from 924 pediatric AML patients in a discovery cohort and validated findings in 159 patients.
Evaluated 2296 variable CpG sites linked to pharmacokinetic/pharmacodynamic and AML-related genes.
Used Cox proportional hazards and logistic regression to assess associations with event-free survival, overall survival, and measurable residual disease.
Identified 23 CpG sites in PK/PD genes and 42 CpG sites in AML-related genes significantly linked to clinical endpoints (p < 2.17 × 10−5).
Hypermethylation of ABCA3, MPO, and MPL was consistently associated with poorer overall survival and event-free survival across cohorts.
Demonstrated inverse correlations between DNA methylation and gene expression for multiple important genes, indicating functional implications.