FLT3 mutations as diagnostic and prognostic biomarkers in acute myeloid leukemia

Acute myeloid leukemia (AML) is a diverse and complex haematological cancer that cannot be fully characterized, even with the combination of morphology and cytogenetics. As a result, molecular biomarkers have become the focus of diagnosis, risk stratification, therapeutic planning and monitoring of disease. Of these, FLT3 mutations have been identified as being clinically relevant, clinically important, and easily detected during various phases of AML care. This review examines the diagnostic, prognostic, predictive and monitoring role of FLT3 mutations in AML, with a focus on the clinical applications in the laboratory. We review the evidence for FLT3 internal tandem duplication (FLT3-ITD) and FLT3 tyrosine kinase domain (FLT3-TKD) mutations, their association with relapse risk, remission duration, survival, response to FLT3 inhibitors and measurable residual disease testing. The impact of allelic burden, variant allele frequency, insertion site, structural characteristics, co-mutational background, interpretation of FLT3 results in ELN 2022, and treatment exposure help clarify the clinical significance of FLT3 results. A particular focus is placed on laboratory assay implementation, including PCR-based assays, fragment analysis, next-generation sequencing and droplet digital PCR, as well as assay sensitivity, mutation quantification, structural annotation, and inter-platform standardization. FLT3 should be used as an integrated clinical laboratory biomarker and not a simple mutation-positive or mutation-negative result. Its mutation subtype, molecular context, treatment setting, assay performance and standardized reporting determine its diagnostic, prognostic, predictive and MRD-related value. This review offers a clinical laboratory perspective on how to interpret FLT3 mutations as actionable biomarkers in AML.