Potential mechanisms of active components from traditional Chinese medicine in acute myeloid leukemia via ferroptosis: an integrative bioinformatics and molecular modeling study

Background Acute myeloid leukemia (AML) represents a heterogeneous hematologic malignancy with divergent clinical outcomes. The prognostic significance of ferroptosis-associated genes and bioactive compounds derived from traditional Chinese medicine (TCM) in AML has not been fully characterized. We sought to construct an AML prognostic model by integrating ferroptosis-related genes with TCM molecular targets and to investigate the mechanistic basis underlying their interactions. Methods Transcriptomic data were obtained from TCGA-LAML, GSE114868 (training cohorts) and GSE71014 (validation cohort). Candidate genes were screened by overlapping differentially expressed genes, ferroptosis-related gene sets and TCM target databases. Analyses included prognostic gene selection, model construction and validation, nomogram establishment, immune microenvironment profiling, gene set enrichment analysis (GSEA), Mendelian randomization (MR), molecular docking and molecular dynamics (MD) simulations. Reverse transcription quantitative polymerase chain reaction (RT-qPCR) was used to validate gene expression. Results CDKN1A and HMOX1 were identified as key prognostic genes, and the model showed stable predictive performance. Risk scores were correlated with age, and both genes independently predicted AML prognosis. The high-risk group had an immunosuppressive microenvironment. The two genes were enriched in ferroptosis pathways. MR analysis suggested a potential causal association between CDKN1A and AML (IVW P = 0.0104), whereas HMOX1 did not reach statistical significance (IVW P = 0.109). Quercetin and luteolin showed potential binding to the target proteins. RT-qPCR suggested lower CDKN1A and HMOX1 expression in a small AML cohort; these findings require validation in larger cohorts. Conclusion The CDKN1A and HMOX1 -based prognostic model showed potential for stratifying AML patients in exploratory analyses. TCM bioactive components may target these genes and regulate ferroptosis pathways, but these mechanisms remain hypothetical and require experimental validation.