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01-01-2021 | Original Article

Heterogeneity of the bone marrow niche in patients with myeloproliferative neoplasms: ActivinA secretion by mesenchymal stromal cells correlates with the degree of marrow fibrosis

Authors: Benedetta Rambaldi, Elisa Diral, Samantha Donsante, Noemi Di Marzo, Federica Mottadelli, Lucia Cardinale, Erica Dander, Giuseppe Isimbaldi, Pietro Pioltelli, Andrea Biondi, Mara Riminucci, Giovanna D’Amico, Elena Maria Elli, Alice Pievani, Marta Serafini

Published in: Annals of Hematology | Issue 1/2021

Abstract

Mesenchymal stromal cells (MSCs) represent an essential component of the bone marrow (BM) niche and display disease-specific alterations in several myeloid malignancies. The aim of this work was to study possible MSC abnormalities in Philadelphia-negative myeloproliferative neoplasms (MPNs) in relationship to the degree of BM fibrosis. MSCs were isolated from BM of 6 healthy donors (HD) and of 23 MPN patients, classified in 3 groups according to the diagnosis and the grade of BM fibrosis: polycythemia vera and essential thrombocythemia (PV/ET), low fibrosis myelofibrosis (LF-MF), and high fibrosis MF (HF-MF). MSC cultures were established from 21 of 23 MPN patients. MPN-derived MSCs did not exhibit any functional impairment in their adipogenic/osteogenic/chondrogenic differentiation potential and displayed a phenotype similar to HD-derived MSCs but with a decreased expression of CD146. All MPN-MSC lines were negative for the patient-specific hematopoietic clone mutations (JAK2, MPL, CALR). MSCs derived from HF-MF patients displayed a reduced clonogenic potential and a lower growth kinetic compared to MSCs from HD, LF-MF, and PV/ET patients. mRNA levels of hematopoiesis regulatory molecules were unaffected in MSCs from HF-MF compared to HD. Finally, in vitro ActivinA secretion by MSCs was increased in HF-MF compared to LF-MF patients, in association with a lower hemoglobin value. Increased ActivinA immunolabeling on stromal cells and erythroid precursors was also observed in HF-MF BM biopsies. In conclusion, higher grade of BM fibrosis is associated with functional impairment of MSCs and the increased secretion of ActivinA may represent a suitable target for anemia treatment in MF patients.

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Title: Heterogeneity of the bone marrow niche in patients with myeloproliferative neoplasms: ActivinA secretion by mesenchymal stromal cells correlates with the degree of marrow fibrosis
Authors: Benedetta Rambaldi
Elisa Diral
Samantha Donsante
Noemi Di Marzo
Federica Mottadelli
Lucia Cardinale
Erica Dander
Giuseppe Isimbaldi
Pietro Pioltelli
Andrea Biondi
Mara Riminucci
Giovanna D’Amico
Elena Maria Elli
Alice Pievani
Marta Serafini
Publication date: 01-01-2021
Publisher: Springer Berlin Heidelberg
Published in: Annals of Hematology / Issue 1/2021
Print ISSN: 0939-5555
Electronic ISSN: 1432-0584
DOI: https://doi.org/10.1007/s00277-020-04306-w

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Heterogeneity of the bone marrow niche in patients with myeloproliferative neoplasms: ActivinA secretion by mesenchymal stromal cells correlates with the degree of marrow fibrosis

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