Profiling of circulating exosomal miRNAs in patients with Waldenström Macroglobulinemia

• Published in: PloS one 2018-10, Vol.13 (10), p.e0204589-e0204589
• Main Authors: Bouyssou, Juliette M, Liu, Chia-Jen, Bustoros, Mark, Sklavenitis-Pistofidis, Romanos, Aljawai, Yosra, Manier, Salomon, Yosef, Amir, Sacco, Antonio, Kokubun, Katsutoshi, Tsukamoto, Shokichi, Perilla Glen, Adriana, Huynh, Daisy, Castillo, Jorge J, Treon, Steven P, Leblond, Véronique, Hermine, Olivier, Roccaro, Aldo M, Ghobrial, Irene M, Capelletti, Marzia
• Format: Article
• Language: English
• Subjects: Adult; Aged; Analysis; Anticoagulants; B-cell lymphoma; Bioindicators; Biology and life sciences; Biomarkers; Biomarkers - blood; Bone marrow; Cancer; Care and treatment; Cell Line; Development and progression; Disease control; Disease Progression; Environmental changes; Exosomes; Female; Gene Expression Regulation, Neoplastic; Hematology; Humans; Immunoglobulin M; Lymphocytes B; Lymphoma; Macroglobulinemia; Male; Medical research; Medical schools; Medicine and Health Sciences; Medicine, Experimental; Metastasis; MicroRNA; MicroRNAs; MicroRNAs - blood; MicroRNAs - genetics; Middle Aged; miRNA; Multiple myeloma; Non-Hodgkin's lymphomas; Oncology; Pathogenesis; Patients; Peripheral blood; Proteins; Research and analysis methods; Smoldering; Therapeutic applications; Tumor suppressor genes; Tumors; Waldenstrom Macroglobulinemia - blood; Waldenstrom Macroglobulinemia - genetics
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0204589

Waldenström Macroglobulinemia (WM) is a low-grade B-cell lymphoma characterized by disease progression from IgM MGUS to asymptomatic and then symptomatic disease states. We profiled exosomes from the peripheral blood of patients with WM at different stages (30 smoldering/asymptomatic WM, 44 symptomatic WM samples and 10 healthy controls) to define their role as potential biomarkers of disease progression. In this study, we showed that circulating exosomes and their miRNA content represent unique markers of the tumor and its microenvironment. We observed similar levels of miRNAs in exosomes from patients with asymptomatic (smoldering) and symptomatic WM, suggesting that environmental and clonal changes occur in patients at early stages of disease progression before symptoms occur. Moreover, we identified a small group of miRNAs whose expression correlated directly or inversely with the disease status of patients, notably the known tumor suppressor miRNAs let-7d and the oncogene miR-21 as well as miR-192 and miR-320b. The study of these miRNAs' specific effect in WM cells could help us gain further insights on the mechanisms underlying WM pathogenesis and reveal their potential as novel therapeutic targets for this disease.