PTGER4 promoter methylation may serve as an independent prognostic biomarker and is associated with response to hypomethylating agents in pediatric acute myeloid leukemia
TL;DR
PTGER4 promoter methylation is a promising prognostic biomarker for pediatric AML and correlates with improved response to HMAs, and could help refine risk stratification and guide individualized treatment decisions, particularly in patients with baseline thrombocytopenia.
Abstract
Background Despite advances in therapy, 30%–40% of pediatric acute myeloid leukemia (AML) patients still experience treatment failure due to relapse or toxicity. Current risk stratification based on genetic features remains insufficient, and epigenetic biomarkers for pediatric AML are understudied. This study aimed to evaluate the prognostic and predictive value of PTGER4, SHOX2, and HOXA9 promoter methylation in pediatric AML. Methods We enrolled 69 newly diagnosed pediatric AML patients treated with standardized chemotherapy. Promoter methylation levels were measured by multiplex methylation-specific PCR. Associations between methylation status and clinical characteristics, survival outcomes, and response to hypomethylating agents (HMAs) were analyzed using univariate and multivariate Cox regression, sensitivity analyses, and subgroup validation. Results Methylation levels of all three genes were significantly associated with age and core binding factor abnormalities. PTGER4 methylation positivity was identified as an independent adverse prognostic factor for event-free survival (hazard ratio (HR) = 3.456, 95% CI 1.126–10.610, P = 0.030), with a significant dose-response relationship between methylation levels and survival. Subgroup analyses confirmed its prognostic value in patients with platelet count <50 × 109/L, those achieving complete remission (CR) after induction and patients within transplant group. Among PTGER4 methylation-positive patients, HMA-based therapy was associated with significantly improved 3-year overall survival (84.6% vs. 19.0%, P = 0.011). Conclusion PTGER4 promoter methylation is a promising prognostic biomarker for pediatric AML and correlates with improved response to HMAs. It could help refine risk stratification and guide individualized treatment decisions, particularly in patients with baseline thrombocytopenia and those achieving post-induction CR or receiving transplant.