MOLECULAR MARKERS IN AML: PROGNOSTC IMPLICATIONS AND IMPACT ON TREATMENT DECISION-MAKING

Acute myeloid leukemia (AML) is a biologically heterogeneous hematologic malignancy in which recurrent cytogenetic and molecular abnormalities critically influence diagnostic classification, prognosis, therapeutic allocation, measurable residual disease (MRD) assessment, and relapse biology. Over the last decade, next-generation sequencing (NGS) has profoundly expanded the molecular characterization of AML, complementing morphology, immunophenotyping, and cytogenetics and enabling increasingly personalized therapeutic strategies. The European LeukemiaNet (ELN) 2022 recommendations established an integrated cytogenetic-molecular backbone for risk stratification. In contrast, subsequent refinements in the era of hypomethylating agents plus venetoclax demonstrated that molecular risk is increasingly treatment-dependent rather than universally fixed across therapeutic platforms. In parallel, targeted therapies against FLT3, IDH1/2, BCL2, CD33, and menin-dependent transcriptional programs have profoundly reshaped AML management in both fit and unfit patients. Emerging data further indicate that co-mutational architecture, clonal hierarchy, variant allele frequency, and MRD kinetics may refine prognostic assessment beyond traditional single-gene models. Consequently, modern AML management increasingly relies on dynamic molecular interpretation integrating baseline genomics with treatment response and longitudinal disease monitoring. This review discusses the current prognostic and predictive role of major molecular markers in AML, focusing on FLT3-mutated AML, IDH1/2-mutated AML, NPM1-mutated AML, TP53-mutated disease, KIT-mutated core-binding factor AML, and KMT2A/NUP98-driven leukemias, together with treatment-dependent risk stratification, co-mutational refinement, menin inhibitors, germline predisposition syndromes, and MRD-guided therapeutic adaptation. The central concept is that molecular abnormalities should no longer be considered static prognostic labels, but rather operational biomarkers capable of guiding time-sensitive clinical decisions from diagnosis through post-transplant surveillance and relapse management