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Involvement of MAF/SPP1 axis in the development of bone marrow fibrosis in PMF patients

Primary myelofibrosis (PMF) is a myeloproliferative neoplasm characterized by hyperplastic megakaryopoiesis and myelofibrosis. We recently described the upregulation of MAF (v-maf avian musculoaponeurotic fibrosarcoma oncogene homolog) in PMF CD34+ hematopoietic progenitor cells (HPCs) compared to h...

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Autores principales: Ruberti, S, Bianchi, E, Guglielmelli, P, Rontauroli, S, Barbieri, G, Tavernari, L, Fanelli, T, Norfo, R, Pennucci, V, Fattori, G Corbizi, Mannarelli, C, Bartalucci, N, Mora, B, Elli, L, Avanzini, M A, Rossi, C, Salmoiraghi, S, Zini, R, Salati, S, Prudente, Z, Rosti, V, Passamonti, F, Rambaldi, A, Ferrari, S, Tagliafico, E, Vannucchi, A M, Manfredini, R
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5808097/
https://www.ncbi.nlm.nih.gov/pubmed/28745329
http://dx.doi.org/10.1038/leu.2017.220
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author Ruberti, S
Bianchi, E
Guglielmelli, P
Rontauroli, S
Barbieri, G
Tavernari, L
Fanelli, T
Norfo, R
Pennucci, V
Fattori, G Corbizi
Mannarelli, C
Bartalucci, N
Mora, B
Elli, L
Avanzini, M A
Rossi, C
Salmoiraghi, S
Zini, R
Salati, S
Prudente, Z
Rosti, V
Passamonti, F
Rambaldi, A
Ferrari, S
Tagliafico, E
Vannucchi, A M
Manfredini, R
author_facet Ruberti, S
Bianchi, E
Guglielmelli, P
Rontauroli, S
Barbieri, G
Tavernari, L
Fanelli, T
Norfo, R
Pennucci, V
Fattori, G Corbizi
Mannarelli, C
Bartalucci, N
Mora, B
Elli, L
Avanzini, M A
Rossi, C
Salmoiraghi, S
Zini, R
Salati, S
Prudente, Z
Rosti, V
Passamonti, F
Rambaldi, A
Ferrari, S
Tagliafico, E
Vannucchi, A M
Manfredini, R
author_sort Ruberti, S
collection PubMed
description Primary myelofibrosis (PMF) is a myeloproliferative neoplasm characterized by hyperplastic megakaryopoiesis and myelofibrosis. We recently described the upregulation of MAF (v-maf avian musculoaponeurotic fibrosarcoma oncogene homolog) in PMF CD34+ hematopoietic progenitor cells (HPCs) compared to healthy donor. Here we demonstrated that MAF is also upregulated in PMF compared with the essential thrombocytemia (ET) and polycytemia vera (PV) HPCs. MAF overexpression and knockdown experiments shed some light into the role of MAF in PMF pathogenesis, by demonstrating that MAF favors the megakaryocyte and monocyte/macrophage commitment of HPCs and leads to the increased expression of proinflammatory and profibrotic mediators. Among them, we focused our further studies on SPP1 and LGALS3. We assessed SPP1 and LGALS3 protein levels in 115 PMF, 47 ET and 24 PV patients plasma samples and we found that SPP1 plasma levels are significantly higher in PMF compared with ET and PV patients. Furthermore, in vitro assays demonstrated that SPP1 promotes fibroblasts and mesenchymal stromal cells proliferation and collagen production. Strikingly, clinical correlation analyses uncovered that higher SPP1 plasma levels in PMF patients correlate with a more severe fibrosis degree and a shorter overall survival. Collectively our data unveil that MAF overexpression contributes to PMF pathogenesis by driving the deranged production of the profibrotic mediator SPP1.
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spelling pubmed-58080972018-02-14 Involvement of MAF/SPP1 axis in the development of bone marrow fibrosis in PMF patients Ruberti, S Bianchi, E Guglielmelli, P Rontauroli, S Barbieri, G Tavernari, L Fanelli, T Norfo, R Pennucci, V Fattori, G Corbizi Mannarelli, C Bartalucci, N Mora, B Elli, L Avanzini, M A Rossi, C Salmoiraghi, S Zini, R Salati, S Prudente, Z Rosti, V Passamonti, F Rambaldi, A Ferrari, S Tagliafico, E Vannucchi, A M Manfredini, R Leukemia Original Article Primary myelofibrosis (PMF) is a myeloproliferative neoplasm characterized by hyperplastic megakaryopoiesis and myelofibrosis. We recently described the upregulation of MAF (v-maf avian musculoaponeurotic fibrosarcoma oncogene homolog) in PMF CD34+ hematopoietic progenitor cells (HPCs) compared to healthy donor. Here we demonstrated that MAF is also upregulated in PMF compared with the essential thrombocytemia (ET) and polycytemia vera (PV) HPCs. MAF overexpression and knockdown experiments shed some light into the role of MAF in PMF pathogenesis, by demonstrating that MAF favors the megakaryocyte and monocyte/macrophage commitment of HPCs and leads to the increased expression of proinflammatory and profibrotic mediators. Among them, we focused our further studies on SPP1 and LGALS3. We assessed SPP1 and LGALS3 protein levels in 115 PMF, 47 ET and 24 PV patients plasma samples and we found that SPP1 plasma levels are significantly higher in PMF compared with ET and PV patients. Furthermore, in vitro assays demonstrated that SPP1 promotes fibroblasts and mesenchymal stromal cells proliferation and collagen production. Strikingly, clinical correlation analyses uncovered that higher SPP1 plasma levels in PMF patients correlate with a more severe fibrosis degree and a shorter overall survival. Collectively our data unveil that MAF overexpression contributes to PMF pathogenesis by driving the deranged production of the profibrotic mediator SPP1. Nature Publishing Group 2018-02 2017-08-08 /pmc/articles/PMC5808097/ /pubmed/28745329 http://dx.doi.org/10.1038/leu.2017.220 Text en Copyright © 2018 The Author(s) http://creativecommons.org/licenses/by-nc-nd/4.0/ This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-nd/4.0/
spellingShingle Original Article
Ruberti, S
Bianchi, E
Guglielmelli, P
Rontauroli, S
Barbieri, G
Tavernari, L
Fanelli, T
Norfo, R
Pennucci, V
Fattori, G Corbizi
Mannarelli, C
Bartalucci, N
Mora, B
Elli, L
Avanzini, M A
Rossi, C
Salmoiraghi, S
Zini, R
Salati, S
Prudente, Z
Rosti, V
Passamonti, F
Rambaldi, A
Ferrari, S
Tagliafico, E
Vannucchi, A M
Manfredini, R
Involvement of MAF/SPP1 axis in the development of bone marrow fibrosis in PMF patients
title Involvement of MAF/SPP1 axis in the development of bone marrow fibrosis in PMF patients
title_full Involvement of MAF/SPP1 axis in the development of bone marrow fibrosis in PMF patients
title_fullStr Involvement of MAF/SPP1 axis in the development of bone marrow fibrosis in PMF patients
title_full_unstemmed Involvement of MAF/SPP1 axis in the development of bone marrow fibrosis in PMF patients
title_short Involvement of MAF/SPP1 axis in the development of bone marrow fibrosis in PMF patients
title_sort involvement of maf/spp1 axis in the development of bone marrow fibrosis in pmf patients
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5808097/
https://www.ncbi.nlm.nih.gov/pubmed/28745329
http://dx.doi.org/10.1038/leu.2017.220
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