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Ferrata Storti Foundation
Haematologica 2021 Volume 106(12):3162-3169
Bone marrow megakaryocytic activation predicts fibrotic evolution of Philadelphia-negative myeloproliferative neoplasms
Mattia Schino,1* Vincenzo Fiorentino,1* Elena Rossi,2,3 Silvia Betti,3 Monica Di Cecca,2 Valentina Ranucci,1 Patrizia Chiusolo,2,3
Maurizio Martini,1,3# Valerio De Stefano2,3# and Luigi Maria Larocca1,3#
1Department of Life Sciences and Public Health, Università Cattolica del Sacro Cuore; 2Department of Radiological and Hematological Sciences, Università Cattolica del Sacro Cuore and 3Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy
*MF and VF contributed equally as co-first authors.
#VDS, MM and LML contributed equally as co-senior authors.
ABSTRACT
Philadelphia-negative chronic myeloproliferative neoplasms (MPN) have been traditionally considered as indistinctly slowly progress- ing conditions; recent evidence proves that a subset of cases have a rapid evolution, so that MPN prognosis needs to be personalized. We identified a new morphological parameter, defined as megakaryocytic activation (M-ACT) based on the coexistence of megakaryocytic emperipolesis, megakaryocytes (MK) cluster formation and evidence of arrangement of collagen fibers around the perimeter of MK. We retro- spectively analyzed the bone marrow biopsy of two MPN cohorts of patients with polycythemia (PV) (n=64) and non-PV patients (including essential thrombocythemia, and early/prefibrotic primary myelofibrosis [PMF]) (n=222). M-ACT showed a significant correlation with splenomegaly, white blood cell count, and lactate dehydrogenase serum levels in both groups, with JAK2 V617F allele burden in PV patients, and with CALR mutations, and platelet count in non-PV patients. Progression-free survival, defined as PV-to-secondary MF progression and non-PV-to-overt PMF, was worse in both PV and early/prefibrotic PMF patients with M-ACT in comparison to those without M-ACT (P<0.0001). Interestingly, M-ACT was not found in the subgroup of essential thrombocythemia patients. In conclusion, M-ACT can be help- ful in the differential diagnosis of MPN and can represent a new morpho- logic parameter with a predictive value for progression of MPN.
Introduction
Philadelphia-negative chronic myeloproliferative neoplasms (MPN) represent a group of hematological disorders that originates from the neoplastic transformation of a pluripotent stem cell and are characterized by clonal proliferation of one or more hematopoietic progenitors in the bone marrow (BM) and in extramedullary sites.
According to the World Health Organization (WHO) 2017 classification, MPN can be divided into three main sets: polycythemia vera (PV), essential phrombo- cythemia (ET) and primary myelofibrosis (PMF), whose early stages’ differential diagnosis is often challenging.1
While MPN have been traditionally considered as indistinct slow progressing con- ditions,2,3 recent evidence, on the contrary, demonstrated that a subset of cases had a rapid evolution, leading different groups to develop several prognostic scores, mainly based on clinical and laboratory parameters with less emphasis on morpho- logical, immunophenotypic and molecular data.4 The first prognostic score was the International Prognostic Scoring System (IPSS), edited in 2009 by an international
Myeloproliferative Disorders
Correspondence:
LUIGI MARIA LAROCCA
luigimaria.larocca@unicatt.it
Received: June 24, 2020. Accepted: October 2, 2020. Pre-published: November 19, 2020.
https://doi.org/10.3324/haematol.2020.264143 ©2021 Ferrata Storti Foundation
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