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

doi:10.1371/journal.pone.0204589

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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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 language	English (US)
Article number	e0204589
Journal	PloS one
Volume	13
Issue number	10
DOIs	https://doi.org/10.1371/journal.pone.0204589
State	Published - Oct 2018
Externally published	Yes

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Bouyssou, J. M., Liu, C. J., Bustoros, M., Sklavenitis-Pistofidis, R., Aljawai, Y., Manier, S., Yosef, A., Sacco, A., Kokubun, K., Tsukamoto, S., Glen, A. P., Huynh, D., Castillo, J. J., Treon, S. P., Leblond, V., Hermine, O., Roccaro, A. M., Ghobrial, I. M., & Capelletti, M. (2018). Profiling of circulating exosomal miRNAs in patients with Waldenström Macroglobulinemia. PloS one, 13(10), Article e0204589. https://doi.org/10.1371/journal.pone.0204589

Bouyssou, JM, Liu, CJ, Bustoros, M, Sklavenitis-Pistofidis, R, Aljawai, Y, Manier, S, Yosef, A, Sacco, A, Kokubun, K, Tsukamoto, S, Glen, AP, Huynh, D, Castillo, JJ, Treon, SP, Leblond, V, Hermine, O, Roccaro, AM, Ghobrial, IM & Capelletti, M 2018, 'Profiling of circulating exosomal miRNAs in patients with Waldenström Macroglobulinemia', PloS one, vol. 13, no. 10, e0204589. https://doi.org/10.1371/journal.pone.0204589

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title = "Profiling of circulating exosomal miRNAs in patients with Waldenstr{\"o}m Macroglobulinemia",

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.",

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

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AU - Aljawai, Yosra

AU - Manier, Salomon

AU - Yosef, Amir

AU - Sacco, Antonio

AU - Kokubun, Katsutoshi

AU - Tsukamoto, Shokichi

AU - Glen, Adriana Perilla

AU - Huynh, Daisy

AU - Castillo, Jorge J.

AU - Treon, Steven P.

AU - Leblond, Veronique

AU - Hermine, Olivier

AU - Roccaro, Aldo M.

AU - Ghobrial, Irene M.

AU - Capelletti, Marzia

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Profiling of circulating exosomal miRNAs in patients with Waldenström Macroglobulinemia

Abstract

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