Extracellular Vesicle-Based Approaches in Acute Myeloid Leukemia: Therapeutic Potential and Translational Challenges

Acute myeloid leukemia (AML) is an aggressive and heterogeneous hematological malignancy in which treatment resistance and relapse remain major causes of mortality. Extracellular vesicles (EVs) contribute to AML progression by mediating communication among leukemic blasts, leukemia stem cells, hematopoietic stem and progenitor cells, stromal and endothelial cells, and immune-cell populations. Experimental studies indicate that AML-associated EVs can remodel the bone marrow niche, suppress normal hematopoiesis, impair antileukemic immune responses, promote leukemic-cell survival, and facilitate drug resistance. Their surface markers and molecular cargo, including proteins, miRNAs, mRNAs, DNA, lipids, and metabolites, have also prompted investigation into their use as liquid-biopsy biomarkers. Candidate EV-based markers include particle abundance, blast-associated antigens, TGF-β1, FLT3-ITD and NPM1 alterations, and several circulating miRNAs. However, most biomarker studies remain small, heterogeneous, and insufficiently compared with established measurable residual disease assays. Therapeutic strategies involving inhibition of EV release or uptake, EV-based immunotherapy, and engineered EVs for drug or RNA delivery are also being explored, but current evidence is predominantly preclinical. Clinical translation is further limited by inconsistent terminology, variable isolation and characterization methods, contamination by non-vesicular particles, and a lack of prospective multicenter validation. This review summarizes the biological roles, biomarker potential, therapeutic applications, and methodological challenges of EVs in AML and highlights the priorities required for their future clinical development.