An update on extracellular vesicles in hematologic disorders: molecular mediators, clinical biomarkers, and emerging therapeutics.

Extracellular vesicles (EVs) are nanosized particles secreted by various cell types. These vesicles play vital roles in intercellular communication and carry diverse cargos of bioactive molecules. In hematological malignancies, EV-associated miRNAs (e.g., miR-21, miR-155) and proteins (e.g., CD30, TGF-β1) act as non-invasive biomarkers for leukemia and lymphoma, surpassing traditional methods in sensitivity. In myelodysplastic syndromes (MDS), EVs containing dysregulated miR-10a and miR-15a are linked to disease progression. Prognostically, EV levels and cargo composition help predict treatment response and relapse risk, as demonstrated in acute myeloid leukemia (AML), where increased miR-10b in EVs relates to poorer survival. Beyond cancers, EVs also contribute to coagulation disorders, sickle cell disease, and other hematological conditions by modifying cellular interactions and signaling pathways. The diagnostic potential of EVs lies in their disease-specific molecular content. Therapeutically, EVs present advantages like low immunogenicity and targeted delivery capabilities. Engineered EVs loaded with CRISPR/Cas9 or tumor-suppressor miRNAs (e.g., miR-15a) show promise for gene editing and cancer treatment. Challenges include scalable production, standardization, and minimizing off-target effects, but innovations such as synthetic EV mimetics and hybrid vesicles aim to overcome these issues. They serve as biomarkers for early detection and prognosis, offering valuable insights into disease mechanisms. Their unique physical and chemical properties, along with their pro-tumor effects, make them promising biomarkers, therapeutic targets, and drug delivery platforms. By summarizing their roles in disease pathogenesis and clinical applications, this work emphasizes the significance of EVs in enhancing understanding and treatment of hematological disorders.