Advances in measurable residual disease assessment for acute myeloid leukemia: from cytogenetics and molecular biology to assessment of the methylation pattern and surface-enhanced Raman scattering as emerging technologies

Abstract Measurable residual disease (MRD) assessment has become a cornerstone in the management of acute myeloid leukemia (AML), offering critical prognostic information and guiding post-remission therapy. Conventional MRD detection methods, including multiparameter flow cytometry (MFC), quantitative PCR (qPCR), and next-generation sequencing (NGS), have demonstrated strong predictive value but are limited by technical complexity, marker specificity, and accessibility. This review explores the current landscape of MRD monitoring in AML, covering cytogenetic, immunophenotypic, and molecular approaches, with particular emphasis on the strengths and limitations of each. We further examine promising emerging technologies—namely DNA methylation profiling and surface-enhanced Raman scattering (SERS)—as non-invasive alternatives. DNA methylation-based assays capitalize on the epigenetic dysregulation characteristic of AML, while proof-of-concept studies indicate SERS as a promising alternative for cancer subtypes, stages or specific mutation detection by analyzing biofluids or extracted DNA from blood. Together, these developments hold the potential to overcome current diagnostic limitations, enabling more universal and precise MRD assessment. Ongoing research and validation will determine their future integration into standard clinical practice.