Antonella Caivano1, Francesco La Rocca2, Vittorio Simeon2, Marco Girasole3, Simone Dinarelli3, Ilaria Laurenzana2, Angelo De Stradis4, Luciana De Luca2, Stefania Trino2, Antonio Traficante5, Giovanni D'Arena6, Giovanna Mansueto6, Oreste Villani6, Giuseppe Pietrantuono6, Luca Laurenti7, Luigi Del Vecchio8, Pellegrino Musto9. 1. Laboratory of Preclinical and Translational Research, IRCCS-Referral Cancer Center of Basilicata (CROB), 85028, Rionero in Vulture, Potenza, Italy. caivanoa@libero.it. 2. Laboratory of Preclinical and Translational Research, IRCCS-Referral Cancer Center of Basilicata (CROB), 85028, Rionero in Vulture, Potenza, Italy. 3. Institute for the Study of the Structure of Matter, National Research Council (CNR), Rome, Italy. 4. Institute for Sustainable Plant Protection, CNR, Bari, Italy. 5. Unit of Clinical Pathology, IRCCS-CROB, Rionero in Vulture, Potenza, Italy. 6. Department of Onco-Hematology, IRCCS-CROB, Rionero in Vulture, Potenza, Italy. 7. Department of Hematology, Catholic University of the Sacred Heart, Rome, Italy. 8. CEINGE-Biotecnologie Avanzate scarl and Department of Molecular Medicine and Medical Biotechnologies, Federico II University, Naples, Italy. 9. Scientific Direction, IRCCS-CROB, Rionero in Vulture, Potenza, Italy.
Abstract
PURPOSE: 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. CONCLUSION: Our data indicate that EV miR155 may serve as an attractive new, non-invasive diagnostic biomarker in human hematologic malignancies.
PURPOSE: 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 cancerpatients. 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 AMLpatients. CONCLUSION: Our data indicate that EV miR155 may serve as an attractive new, non-invasive diagnostic biomarker in humanhematologic malignancies.
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