Profiling of circulating exosomal miRNAs in patients with Waldenström Macroglobulinemia

Juliette M. Bouyssou, Chia Jen Liu, Mark Bustoros, Romanos Sklavenitis-Pistofidis, Yosra Aljawai, Salomon Manier, Amir Yosef, Antonio Sacco, Katsutoshi Kokubun, Shokichi Tsukamoto, Adriana Perilla Glen, Daisy Huynh, Jorge J. Castillo, Steven P. Treon, Veronique Leblond, Olivier Hermine, Aldo M. Roccaro, Irene M. Ghobrial, Marzia Capelletti

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18 Scopus citations

Abstract

Waldenstrom 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 WMat 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 inWMcells could help us gain further insights on the mechanisms underlying WM pathogenesis and reveal their potential as novel therapeutic targets for this disease.

Original languageEnglish
Article numbere0204589
JournalPLoS ONE
Volume13
Issue number10
DOIs
StatePublished - Oct 2018

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