Multi-omics-guided dynamic precision medicine in leukemia: An AML-centered framework integrating genotype, cellular...

Leukemia comprises a group of hematologic malignancies characterized by pronounced molecular heterogeneity, cellular-state plasticity, and highly variable clinical outcomes. With the rapid development of high-throughput sequencing, single-cell and spatial omics, molecular measurable residual disease monitoring, and immune-engineering technologies, the diagnostic and therapeutic paradigm of leukemia is shifting from conventional morphology- and cytogenetics-based stratification toward dynamic precision medicine driven by multi-omics data. Using acute myeloid leukemia as the core model, this review systematically integrates evidence from genomics, epigenomics, transcriptomics, proteomics, metabolomics, and spatial omics to elucidate the coordinated roles of driver mutations, epigenetic regulation, leukemia stem cell plasticity, clonal evolution, the bone marrow niche, and the immune microenvironment in disease classification, risk assessment, therapeutic tolerance, and relapse. Key molecular events, including FLT3, NPM1, TP53, IDH1/2, KMT2A rearrangements, and menin-dependent pathways, have substantially advanced targeted therapy and risk-adapted management. However, single genetic abnormalities alone are insufficient to fully explain treatment response and long-term prognosis. By contrast, a multidimensional framework integrating dynamic MRD status, cellular-state transitions, functional drug vulnerabilities, and immune-ecological features may better identify relapse risk, optimize treatment sequencing, and guide the individualized application of CAR-T/CAR-NK therapy, epigenetic therapy, and combination immunotherapeutic strategies. Although multi-omics data integration, assay standardization, clinical accessibility, algorithmic interpretability, and prospective validation remain major challenges, single-cell and spatial omics, AI-assisted decision-making, and digital predictive models are expected to further promote the transition of precision medicine in leukemia from static classification to real-time monitoring, predictive modeling, and adaptive intervention. Overall, the central goal of precision medicine in leukemia is not simply to identify more molecular abnormalities, but to translate multidimensional biological information into a clinically verifiable, actionable, and continuously optimizable decision-making system.