Plasma small-extracellular vesicles enriched in miR-122-5p promote disease aggressiveness in pediatric Anaplastic Large Cell Lymphoma

Emerging evidence shows that small extracellular vesicles (S-EVs) play a critical role in cancer biology. However, the role of S-EVs in pediatric anaplastic large cell lymphoma (ALCL) is still largely unknown. Small RNA sequencing of plasma S-EVs revealed a peculiar microRNA profile in pediatric ALCL patients compared to healthy donors (HD). In particular, the liver-specific miR-122-5p was more abundant in ALCL plasma S-EVs compared to HD. Elevated levels of miR-122-5p correlated with advanced stage disease and impaired hepatic function in ALCL patients. In vitro experiments demonstrated that miR-122-5p inhibits glucose consumption in stromal cells, and the increased glucose availability enhances ALCL cell aggressiveness. Moreover, miR-122-5p promoted tumor dissemination in vivo. This study identified a new molecular factor promoting ALCL cell dissemination. This finding sets the ground for investigating the clinical use of miR-122-5p antagonists in ALCL patients to potentially improve the clinical outcome. Overall design: Comparative gene expression profiling analysis of small RNA-seq data for plasma small extracellular vesicle (S-EV) samples and paired tumor biopsies at diagnosis from 20 paediatric ALCL patients. Patient follow-up resulted in 14 complete remission and 6 relapsed patients. Plus, five samples from healthy donor plasma S-EVs (HD), and S-EVs from Karpas299, MAC2A, SR786, SUDHL1, and SUPM2 cell lines.