{"doi":"10.1002/hon.70093_30","title":"30 | EXOSOMES AND MIRS IN CHILDHOOD NHL AND HODGKIN’S LYMPHOMA","abstract":"Exosomes are small extracellular vesicles released by cells that play a crucial role in intercellular communication. They carry molecular cargo such as proteins, lipids, and nucleic acids, including microRNAs (miRNAs), which can regulate gene expression in recipient cells. Exosomes are present in various body fluids, making them attractive candidates for liquid biopsy—a minimally invasive diagnostic approach that analyzes circulating biomarkers. Liquid biopsy using exosomes and their miRNA content is particularly promising for cancer diagnosis and monitoring, as the exosomal cargo reflects the molecular profile of the tumor cells. This approach holds significant potential in pediatric cancers, where conventional biopsies can be challenging and repeated sampling is often necessary to monitor treatment response and disease progression. In anaplastic large cell lymphoma (ALCL), the liver-specific miR-122-5p was more abundant in patient plasma exosomes than healthy donors, suggesting a non-tumoral origin. Elevated miR-122-5p levels correlated with advanced disease stage and impaired liver 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. Furthermore, miR-122-5p promoted tumor dissemination in vivo, indicating that increased miR-122-5p in circulating exosomes can promote cancer cell dissemination by inducing metabolic changes in the pre-metastatic niche. In addition, small-RNA-sequencing analysis on plasmatic exosomes at diagnosis revealed a specific miRNA cargo in relapsed patients compared to non-relapsed, with seven miRNAs enriched in s-EVs of relapsed patients. MiR-146a-5p and miR-378a-3p showed a negative prognostic impact, possibly representing, together with let-7g-5p, a miRNA panel for the early identification of high-risk patients. MiR-146a-5p was found to promote M2 macrophage polarization, which enhanced ALCL aggressiveness, suggesting a role for tumor-associated macrophages in disease progression. Also in classical Hodgkin lymphoma, the plasma exosome microRNA profile was recently characterized by small RNA sequencing. It was found that the levels of miR-122-5p at diagnosis were significantly higher in patients who relapsed compared to patients in remission. The 5-year event-free survival of cases with high and low levels of miR-122-5p was 65 ± 7% and 93 ± 4%, respectively. MiR-122-5p levels were significantly associated with clinical events in both univariate and multivariate analysis. Target prediction analysis suggests an involvement in the polarization of immune cells. These findings highlight the potential of exosomal miRNA profiling from liquid biopsies as a minimally invasive approach for risk stratification, monitoring treatment response, and gaining insights into disease mechanisms in pediatric lymphomas. Research funding declaration: nothing to declare Keywords: non-Hodgkin (Pediatric, Adolescent, and Young Adult) No potential sources of conflict of interest.","journal":"Hematological Oncology","year":2025,"id":568579,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9444,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1082660,"name":"Lara Mussolin","orcid":"0000-0003-4802-1866","position":0,"is_corresponding":true}],"reference_count":0,"raw_metadata":null,"created_at":"2026-07-19T02:56:52.212268Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}