Profiling of circulating exosomal miRNAs in patients with Waldenström Macroglobulinemia

PLoS One. 2018 Oct 4;13(10):e0204589. doi: 10.1371/journal.pone.0204589. eCollection 2018.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Biomarkers / blood
  • Cell Line
  • Disease Progression
  • Exosomes
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Male
  • MicroRNAs / blood*
  • MicroRNAs / genetics
  • Middle Aged
  • Waldenstrom Macroglobulinemia / blood*
  • Waldenstrom Macroglobulinemia / genetics

Substances

  • Biomarkers
  • MicroRNAs

Grant support

This work was supported by a grant awarded by the International Waldenström's Macroglobulinemia Foundation, https://www.iwmf.com/. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.