Harnessing the power of exosomes in leukemia: from molecular messengers to clinical applications.

Exosomes, nanosized extracellular vesicles (30-150 nm), have emerged as pivotal mediators in leukemia pathogenesis, fundamentally altering our understanding of the disease and therapeutic approaches. These membrane-bound carriers transport complex molecular cargos, including proteins, nucleic acids, and lipids, facilitating intercellular communication that drives malignant transformation, treatment resistance, and remodeling of the bone marrow microenvironment. In leukemia, exosomes orchestrate angiogenesis, immune evasion, and disruption of normal hematopoiesis while serving as repositories of disease-specific biomarkers. Characteristic molecular signatures have been identified across various leukemia subtypes, including microRNA patterns (miR-155, miR-150 in CLL; miR-26a-5p in AML) and protein markers (IFITM3, CD146 in CML), which enable minimally invasive liquid biopsy-based diagnostics and real-time disease monitoring with high sensitivity and specificity. Therapeutically, exosomes function as natural drug delivery vehicles with inherent biocompatibility and barrier-crossing capabilities, while engineered platforms, including CAR-T cell-derived exosomes, offer novel immunotherapeutic strategies. Paradoxically, exosomes also mediate treatment resistance through intercellular transfer of resistant phenotypes, particularly in imatinib-resistant CML and chemoresistant AML, revealing both challenges and therapeutic targets. Clinical translation faces significant hurdles, including standardization of isolation protocols, optimization of cargo loading, scalable manufacturing, and regulatory framework development. The convergence of enhanced biological understanding, technological innovation, and evolving regulatory landscapes positions exosome-based strategies to revolutionize leukemia management through precision diagnostics and targeted therapies with reduced systemic toxicity.