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Tumor Biology

, Volume 36, Issue 12, pp 9739–9752 | Cite as

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

  • Antonella Caivano
  • Ilaria Laurenzana
  • Luciana De Luca
  • Francesco La Rocca
  • Vittorio Simeon
  • Stefania Trino
  • Fiorella D’Auria
  • Antonio Traficante
  • Maddalena Maietti
  • Tiziana Izzo
  • Giovanni D’Arena
  • Giovanna Mansueto
  • Giuseppe Pietrantuono
  • Luca Laurenti
  • Pellegrino Musto
  • Luigi Del Vecchio
Research Article

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.

Keywords

Extracellular vesicles Microvesicles Hematological malignancies Flow cytometry 

Notes

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.

Supplementary material

13277_2015_3741_MOESM1_ESM.xls (13 kb)
ESM. 1 (XLS 13 kb)
13277_2015_3741_MOESM2_ESM.pdf (83 kb)
ESM. 2 (PDF 83 kb)

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Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2015

Authors and Affiliations

  • Antonella Caivano
    • 1
  • Ilaria Laurenzana
    • 1
  • Luciana De Luca
    • 1
  • Francesco La Rocca
    • 1
  • Vittorio Simeon
    • 1
  • Stefania Trino
    • 1
  • Fiorella D’Auria
    • 2
  • Antonio Traficante
    • 3
  • Maddalena Maietti
    • 3
  • Tiziana Izzo
    • 4
  • Giovanni D’Arena
    • 4
  • Giovanna Mansueto
    • 4
  • Giuseppe Pietrantuono
    • 4
  • Luca Laurenti
    • 5
  • Pellegrino Musto
    • 6
  • Luigi Del Vecchio
    • 7
    • 8
  1. 1.Laboratory of Preclinical and Translational ResearchIRCCS-CROBRionero in VultureItaly
  2. 2.Laboratory of Clinical Research and Advanced DiagnosticsIRCCS-CROBRionero in VultureItaly
  3. 3.Unit of Clinical PathologyIRCCS-CROBRionero in VultureItaly
  4. 4.Department of Onco-HematologyIRCCS-CROBRionero in VultureItaly
  5. 5.Department of HematologyCatholic University of the Sacred HeartRomeItaly
  6. 6.Scientific DirectionIRCCS-CROBRionero in VultureItaly
  7. 7.CEINGE-Biotecnologie Avanzate s.c.a.r.l“Federico II” UniversityNaplesItaly
  8. 8.Department of Molecular Medicine and Medical Biotechnology“Federico II” UniversityNaplesItaly

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