Tracking fibrosis in myeloproliferative neoplasms by CCR2 expression on CD34+ cells

In myeloproliferative neoplasm (MPNs), bone marrow fibrosis - mainly driven by the neoplastic megakaryocytic clone - dictates a more severe disease stage with dismal prognosis and higher risk of leukemic evolution. Therefore, accurate patient allocation into different disease categories and timely i...

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Main Authors: Giulia Pozzi, Cecilia Carubbi, Giuliana Gobbi, Sara Tagliaferri, Prisco Mirandola, Marco Vitale, Elena Masselli
Format: Article
Language:English
Published: Frontiers Media S.A. 2022-08-01
Series:Frontiers in Oncology
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fonc.2022.980379/full
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author Giulia Pozzi
Cecilia Carubbi
Giuliana Gobbi
Sara Tagliaferri
Prisco Mirandola
Marco Vitale
Marco Vitale
Elena Masselli
Elena Masselli
author_facet Giulia Pozzi
Cecilia Carubbi
Giuliana Gobbi
Sara Tagliaferri
Prisco Mirandola
Marco Vitale
Marco Vitale
Elena Masselli
Elena Masselli
author_sort Giulia Pozzi
collection DOAJ
description In myeloproliferative neoplasm (MPNs), bone marrow fibrosis - mainly driven by the neoplastic megakaryocytic clone - dictates a more severe disease stage with dismal prognosis and higher risk of leukemic evolution. Therefore, accurate patient allocation into different disease categories and timely identification of fibrotic transformation are mandatory for adequate treatment planning. Diagnostic strategy still mainly relies on clinical/laboratory assessment and bone marrow histopathology, which, however, requires an invasive procedure and frequently poses challenges also to expert hemopathologists. Here we tested the diagnostic accuracy of the detection, by flow cytometry, of CCR2+CD34+ cells to discriminate among MPN subtypes with different degrees of bone marrow fibrosis. We found that the detection of CCR2 on MPN CD34+ cells has a very good diagnostic accuracy for the differential diagnosis between “true” ET and prePMF (AUC 0.892, P<0.0001), and a good diagnostic accuracy for the differential diagnosis between prePMF and overtPMF (AUC 0.817, P=0.0089). Remarkably, in MPN population, the percentage of CCR2-expressing cells parallels the degree of bone marrow fibrosis. In ET/PV patients with a clinical picture suggestive for transition into spent phase, we demonstrated that only patients with confirmed secondary MF showed significantly higher levels of CCR2+CD34+ cells. Overall, flow cytometric CCR2+CD34+ cell detection can be envisioned in support of conventional bone marrow histopathology in compelling clinical scenarios, with the great advantage of being extremely rapid. For patients in follow-up, its role can be conceived as an initial patient screening for subsequent bone marrow biopsy when disease evolution is suspected.
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spelling doaj.art-2f4b440365b34e70b5764c74c57f3d632022-12-22T02:34:42ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2022-08-011210.3389/fonc.2022.980379980379Tracking fibrosis in myeloproliferative neoplasms by CCR2 expression on CD34+ cellsGiulia Pozzi0Cecilia Carubbi1Giuliana Gobbi2Sara Tagliaferri3Prisco Mirandola4Marco Vitale5Marco Vitale6Elena Masselli7Elena Masselli8Department of Medicine and Surgery (DiMeC), University of Parma, Parma, ItalyDepartment of Medicine and Surgery (DiMeC), University of Parma, Parma, ItalyDepartment of Medicine and Surgery (DiMeC), University of Parma, Parma, ItalyDepartment of Medicine and Surgery (DiMeC), University of Parma, Parma, ItalyDepartment of Medicine and Surgery (DiMeC), University of Parma, Parma, ItalyDepartment of Medicine and Surgery (DiMeC), University of Parma, Parma, ItalyParma University Hospital, (AOU-PR), Parma, ItalyDepartment of Medicine and Surgery (DiMeC), University of Parma, Parma, ItalyParma University Hospital, (AOU-PR), Parma, ItalyIn myeloproliferative neoplasm (MPNs), bone marrow fibrosis - mainly driven by the neoplastic megakaryocytic clone - dictates a more severe disease stage with dismal prognosis and higher risk of leukemic evolution. Therefore, accurate patient allocation into different disease categories and timely identification of fibrotic transformation are mandatory for adequate treatment planning. Diagnostic strategy still mainly relies on clinical/laboratory assessment and bone marrow histopathology, which, however, requires an invasive procedure and frequently poses challenges also to expert hemopathologists. Here we tested the diagnostic accuracy of the detection, by flow cytometry, of CCR2+CD34+ cells to discriminate among MPN subtypes with different degrees of bone marrow fibrosis. We found that the detection of CCR2 on MPN CD34+ cells has a very good diagnostic accuracy for the differential diagnosis between “true” ET and prePMF (AUC 0.892, P<0.0001), and a good diagnostic accuracy for the differential diagnosis between prePMF and overtPMF (AUC 0.817, P=0.0089). Remarkably, in MPN population, the percentage of CCR2-expressing cells parallels the degree of bone marrow fibrosis. In ET/PV patients with a clinical picture suggestive for transition into spent phase, we demonstrated that only patients with confirmed secondary MF showed significantly higher levels of CCR2+CD34+ cells. Overall, flow cytometric CCR2+CD34+ cell detection can be envisioned in support of conventional bone marrow histopathology in compelling clinical scenarios, with the great advantage of being extremely rapid. For patients in follow-up, its role can be conceived as an initial patient screening for subsequent bone marrow biopsy when disease evolution is suspected.https://www.frontiersin.org/articles/10.3389/fonc.2022.980379/fullmyeloproliferative neoplasmsmyelofibrosisflow cytometryCCR2biomarkersbone marrow fibrosis
spellingShingle Giulia Pozzi
Cecilia Carubbi
Giuliana Gobbi
Sara Tagliaferri
Prisco Mirandola
Marco Vitale
Marco Vitale
Elena Masselli
Elena Masselli
Tracking fibrosis in myeloproliferative neoplasms by CCR2 expression on CD34+ cells
Frontiers in Oncology
myeloproliferative neoplasms
myelofibrosis
flow cytometry
CCR2
biomarkers
bone marrow fibrosis
title Tracking fibrosis in myeloproliferative neoplasms by CCR2 expression on CD34+ cells
title_full Tracking fibrosis in myeloproliferative neoplasms by CCR2 expression on CD34+ cells
title_fullStr Tracking fibrosis in myeloproliferative neoplasms by CCR2 expression on CD34+ cells
title_full_unstemmed Tracking fibrosis in myeloproliferative neoplasms by CCR2 expression on CD34+ cells
title_short Tracking fibrosis in myeloproliferative neoplasms by CCR2 expression on CD34+ cells
title_sort tracking fibrosis in myeloproliferative neoplasms by ccr2 expression on cd34 cells
topic myeloproliferative neoplasms
myelofibrosis
flow cytometry
CCR2
biomarkers
bone marrow fibrosis
url https://www.frontiersin.org/articles/10.3389/fonc.2022.980379/full
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