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High serum levels of extracellular vesicles expressing malignancy-related markers are released in patients with various types of hematological neoplastic disorders

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Tumor Biology

Abstract

Many cell types release extracellular vesicles (EVs), including exosomes, microvesicles (MVs), and apoptotic bodies, which play a role in physiology and diseases. Presence and phenotype of circulating EVs in hematological malignancies (HMs) remain largely unexplored.

The aim of this study was to characterize EVs in peripheral blood of HM patients compared to healthy subjects (controls). We isolated serum EVs from patients with chronic lymphocytic leukemia (CLL), non-Hodgkin’s lymphoma (NHL), Waldenstrom’s macroglobulinemia (WM), Hodgkin’s lymphoma (HL), multiple myeloma (MM), acute myeloid leukemia (AML), myeloproliferative neoplasms (MPNs), myelodysplastic syndromes (MDS), and controls. EVs were isolated from serum of peripheral blood by ultracentrifuge steps and analyzed by flow cytometry to define count, size, and immunophenotype. MV levels were significantly elevated in WM, HL, MM, AML, and some MPNs and, though at a lesser degree, in CLL and NHL as compared to healthy controls. HL, MM, and MPNs generated a population of MVs characterized by lower size (below 0.3 μm) when compared to controls. MVs from patients specifically expressed tumor-related antigens, such as CD19 in B cell neoplasms, CD38 in MM, CD13 in myeloid tumors, and CD30 in HL. Both total and antigen-specific count of MVs significantly correlated with different HM clinical features such as Rai stage in CLL, International Prognostic Scoring System in WM, International Staging System in MM, and clinical stage in HL. MVs may represent a novel biomarker in HMs.

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Acknowledgments

The study was partially supported by Current Research Funds, Italian Ministry of Health.

No writing assistance was utilized in the production of this manuscript.

Compliance with ethical standards

During the entire investigation period, we followed guidelines and regulations of the Helsinki Declaration, and experiments were approved by the Ethics Committee of IRCCS-CROB (Prot 3 725; 7-2-2008). All patients and controls signed an informed consent form.

Conflicts of interest

No conflicts of interest were declared.

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    Authors and Affiliations

    1. Laboratory of Preclinical and Translational Research, IRCCS-CROB, Via Padre Pio, 1, 85128, Rionero in Vulture, Italy

      Antonella Caivano, Ilaria Laurenzana, Luciana De Luca, Francesco La Rocca, Vittorio Simeon & Stefania Trino

    2. Laboratory of Clinical Research and Advanced Diagnostics, IRCCS-CROB, Via Padre Pio, 1, 85128, Rionero in Vulture, Italy

      Fiorella D’Auria

    3. Unit of Clinical Pathology, IRCCS-CROB, Via Padre Pio, 1, 85128, Rionero in Vulture, Italy

      Antonio Traficante & Maddalena Maietti

    4. Department of Onco-Hematology, IRCCS-CROB, Via Padre Pio, 1, 85128, Rionero in Vulture, Italy

      Tiziana Izzo, Giovanni D’Arena, Giovanna Mansueto & Giuseppe Pietrantuono

    5. Department of Hematology, Catholic University of the Sacred Heart, Rome, Italy

      Luca Laurenti

    6. Scientific Direction, IRCCS-CROB, Via Padre Pio, 1, 85128, Rionero in Vulture, Italy

      Pellegrino Musto

    7. CEINGE-Biotecnologie Avanzate s.c.a.r.l, “Federico II” University, Naples, Italy

      Luigi Del Vecchio

    8. Department of Molecular Medicine and Medical Biotechnology, “Federico II” University, Naples, Italy

      Luigi Del Vecchio

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    1. Antonella Caivano
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    2. Ilaria Laurenzana
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    Correspondence to Antonella Caivano.

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    Pellegrino Musto and Luigi Del Vecchio contributed equally to this work.

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    Caivano, A., Laurenzana, I., De Luca, L. et al. High serum levels of extracellular vesicles expressing malignancy-related markers are released in patients with various types of hematological neoplastic disorders. Tumor Biol. 36, 9739–9752 (2015). https://doi.org/10.1007/s13277-015-3741-3

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