Dual roles of extracellular vesicles in acute lymphoblastic leukemia: implications for disease progression and theranostic strategies.

Acute Lymphoblastic Leukemia (ALL) is a heterogeneous blood cancer characterized by the uncontrolled growth of immature lymphoid cells due to dysregulated signaling pathways. It is the most common pediatric cancer, with high cure rates in children, but significantly lower survival rates in adults. Current theranostic strategies, including chemotherapy, immunotherapy, and nanomedicine, aim to improve detection and treatment precision but are limited by side effects, drug resistance, high costs, and stability issues. Notably, extracellular vesicles (EVs) offer a promising alternative, addressing these limitations through their natural biocompatibility and targeted delivery capabilities. EVs play a dual role in ALL: they contribute to leukemia progression by promoting tumor growth, immune suppression, and drug resistance via the transfer of oncogenic molecules, while also serving as valuable non-invasive biomarkers due to their specific miRNA and protein content. Their ability to deliver therapeutic agents directly to leukemic cells, combined with their stability and low immunogenicity, makes EVs a compelling tool for improving ALL treatments. Indeed, by targeting the molecular pathways influenced by EVs or leveraging them for drug delivery, innovative therapeutic strategies can be developed to enhance treatment outcomes and reduce side effects. Thus, EVs represent a promising frontier for advancing theranostic strategies in ALL, offering new opportunities to improve diagnosis and treatment while overcoming the limitations of traditional therapies. This review will explore the dual roles of EVs in ALL, addressing their contributions to disease progression and their potential as therapeutic agents and biomarkers for early diagnosis and targeted therapies.