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

Profiling of circulating exosomal miRNAs in patients with Waldenström Macroglobulinemia.

Author information

1
Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston MA, United States of America.
2
Université Paris-Saclay / Hôpital Necker-Enfants Malades, Paris, France.
3
Division of Hematology and Oncology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan.
4
School of Medicine, National Yang-Ming University, Taipei, Taiwan.
5
Department of Hematology at Pitié Salpêtrière Hospital, Paris, France.
6
INSERM UMR 1163, Laboratory of Cellular and Molecular Mechanisms of Hematological Disorders and Therapeutic Implications, Paris, France.

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.

PMID:
30286096
PMCID:
PMC6171840
DOI:
10.1371/journal.pone.0204589
[Indexed for MEDLINE]
Free PMC Article

Conflict of interest statement

Irene Ghobrial has a consulting/advisory role with Celgene, Takeda, Bristol-Myers Squibb (BMS), Janssen Pharmaceuticals, and Amgen. Outside of the present study, Irene Ghobrial received research funding/ honoraria from Celgene, Takeda, Bristol-Myers Squibb (BMS), Janssen Pharmaceuticals, and Amgen. This does not alter our adherence to PLOS ONE policies on sharing data and materials. All other authors declare that no competing interests exist.

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