title: MicroRNA-155 in serum-derived extracellular vesicles as a potential biomarker for hematologic malignancies - a short report.
abstract: OBJECTIVE
  The use of extracellular vesicles (EVs) from body fluids as "liquid biopsies" is emerging as a promising approach for the diagnosis, prognosis and therapeutic monitoring of cancer patients. MicroRNA-155 (miR155), a non-coding transcript of the B-cell integration cluster (BIC) gene, has been reported to play a critical role in the pathogenesis of several types of hematologic malignancies (HMs) in which high miR155 levels have been found. At yet, however, the EV miR155 level and its putative clinical relevance in sera of HM patients have not been reported.
  
  
  METHODS
  EVs from sera of representative patients with eight different HMs and healthy subjects (controls) were isolated using differential centrifugation. The identity and quality of the EVs were verified by atomic force and transmission electron microscopy. The EV miR155 levels were measured by quantitative RT-PCR. The sensitivity, specificity and area under the curve (AUC) of differences in EV miR155 levels were determined using ROC curve analyses.
  
  
  RESULTS
  We found that the EV miR155 levels were significantly higher in chronic lymphocytic leukemia (CLL), acute myeloid leukemia (AML) and Waldenström's macroglobulinemia (WM) cases compared to controls. Conversely, we found that the EV miR155 levels were significantly lower in myelodysplastic syndrome (MDS) and multiple myeloma (MM) cases. No differences were found in follicular lymphoma (FL), diffuse large B-cell lymphoma (DLBCL) or Hodgkin's Lymphoma (HL) cases compared to controls. EV miR155 ROC curve analyses revealed significantly different patterns in CLL and AML cases compared to controls, and in AML cases compared to MDS cases (p = 0.004, p = 0.01 and p = 0.04, respectively). In addition, we found that high EV miR155 levels correlated with high white blood cell counts in AML patients.
  
  
  CONCLUSIONS
  Our data indicate that EV miR155 may serve as an attractive new, non-invasive diagnostic biomarker in human hematologic malignancies.
authors.affiliation: Laboratory of Preclinical and Translational Research, IRCCS-Referral Cancer Center of Basilicata (CROB), 85028, Rionero in Vulture, Potenza, Italy. caivanoa@libero.it.
authors.forename: Antonella
authors.identifier: http://orcid.org/0000-0003-2502-4060
authors.initials: A
authors.lastname: Caivano
authors.affiliation: Laboratory of Preclinical and Translational Research, IRCCS-Referral Cancer Center of Basilicata (CROB), 85028, Rionero in Vulture, Potenza, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: La Rocca
authors.affiliation: Laboratory of Preclinical and Translational Research, IRCCS-Referral Cancer Center of Basilicata (CROB), 85028, Rionero in Vulture, Potenza, Italy.
authors.forename: Vittorio
authors.initials: V
authors.lastname: Simeon
authors.affiliation: Institute for the Study of the Structure of Matter, National Research Council (CNR), Rome, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Girasole
authors.affiliation: Institute for the Study of the Structure of Matter, National Research Council (CNR), Rome, Italy.
authors.forename: Simone
authors.initials: S
authors.lastname: Dinarelli
authors.affiliation: Laboratory of Preclinical and Translational Research, IRCCS-Referral Cancer Center of Basilicata (CROB), 85028, Rionero in Vulture, Potenza, Italy.
authors.forename: Ilaria
authors.initials: I
authors.lastname: Laurenzana
authors.affiliation: Institute for Sustainable Plant Protection, CNR, Bari, Italy.
authors.forename: Angelo
authors.initials: A
authors.lastname: De Stradis
authors.affiliation: Laboratory of Preclinical and Translational Research, IRCCS-Referral Cancer Center of Basilicata (CROB), 85028, Rionero in Vulture, Potenza, Italy.
authors.forename: Luciana
authors.initials: L
authors.lastname: De Luca
authors.affiliation: Laboratory of Preclinical and Translational Research, IRCCS-Referral Cancer Center of Basilicata (CROB), 85028, Rionero in Vulture, Potenza, Italy.
authors.forename: Stefania
authors.initials: S
authors.lastname: Trino
authors.affiliation: Unit of Clinical Pathology, IRCCS-CROB, Rionero in Vulture, Potenza, Italy.
authors.forename: Antonio
authors.initials: A
authors.lastname: Traficante
authors.affiliation: Department of Onco-Hematology, IRCCS-CROB, Rionero in Vulture, Potenza, Italy.
authors.forename: Giovanni
authors.initials: G
authors.lastname: D'Arena
authors.affiliation: Department of Onco-Hematology, IRCCS-CROB, Rionero in Vulture, Potenza, Italy.
authors.forename: Giovanna
authors.initials: G
authors.lastname: Mansueto
authors.affiliation: Department of Onco-Hematology, IRCCS-CROB, Rionero in Vulture, Potenza, Italy.
authors.forename: Oreste
authors.initials: O
authors.lastname: Villani
authors.affiliation: Department of Onco-Hematology, IRCCS-CROB, Rionero in Vulture, Potenza, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Pietrantuono
authors.affiliation: Department of Hematology, Catholic University of the Sacred Heart, Rome, Italy.
authors.forename: Luca
authors.initials: L
authors.lastname: Laurenti
authors.affiliation: CEINGE-Biotecnologie Avanzate scarl and Department of Molecular Medicine and Medical Biotechnologies, Federico II University, Naples, Italy.
authors.forename: Luigi
authors.initials: L
authors.lastname: Del Vecchio
authors.affiliation: Scientific Direction, IRCCS-CROB, Rionero in Vulture, Potenza, Italy.
authors.forename: Pellegrino
authors.initials: P
authors.lastname: Musto
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D019540:Area Under Curve; D014408:Biomarkers, Tumor / Q000097:blood*; D000067128:Extracellular Vesicles / Q000235:genetics*; D005260:Female; D019337:Hematologic Neoplasms / Q000097:blood* / Q000235:genetics*; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000097:blood*; D018625:Microscopy, Atomic Force; D046529:Microscopy, Electron, Transmission; D008875:Middle Aged; D012372:ROC Curve; D060888:Real-Time Polymerase Chain Reaction; D012680:Sensitivity and Specificity; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor; C524942:MIRN155 microRNA, human; D035683:MicroRNAs
keywords: Acute myeloid leukemia; Chronic lymphocytic leukemia; Extracellular vesicles; Myelodysplastic syndrome; Waldenström’s macroglobulinemia; miR155