Primary myelofibrosis is characterized by the development of fibrosis in the bone marrow that contributes to ineffective hematopoiesis. Bone marrow fibrosis is the result of a complex and not yet fully understood interaction among megakaryocytes, myeloid cells, fibroblasts, and endothelial cells. Here, we report that >30% of the endothelial cells in the small vessels of the bone marrow and spleen of patients with primary myelofibrosis have a mesenchymal phenotype, which is suggestive of the process known as endothelial-to-mesenchymal transition (EndMT). EndMT can be reproduced in vitro by incubation of cultured endothelial progenitor cells or spleen-derived endothelial cells with inflammatory cytokines. Megakaryocytes appear to be implicated in this process, because EndMT mainly occurs in the microvessels close to these cells, and because megakaryocyte-derived supernatant fluid can reproduce the EndMT switch in vitro. Furthermore, EndMT is an early event in a JAK2-V617F knock-in mouse model of primary myelofibrosis. Overall, these data show for the first time that microvascular endothelial cells in the bone marrow and spleen of patients with primary myelofibrosis show functional and morphologic changes that are associated to the mesenchymal phenotype.

Endothelial-to-Mesenchymal Transition in Bone Marrow and Spleen of Primary Myelofibrosis / Erba, Benedetta Gaia; Gruppi, Cristian; Corada, Monica; Pisati, Federica; Rosti, Vittorio; Bartalucci, Niccoloâ ; Villeval, Jean-Luc; Vannucchi, Alessandro Maria; Barosi, Giovanni; Balduini, Alessandra; Dejana, Elisabetta. - In: THE AMERICAN JOURNAL OF PATHOLOGY. - ISSN 0002-9440. - ELETTRONICO. - 187:(2017), pp. 1879-1892. [10.1016/j.ajpath.2017.04.006]

Endothelial-to-Mesenchymal Transition in Bone Marrow and Spleen of Primary Myelofibrosis

Bartalucci, Niccolo’;Vannucchi, Alessandro Maria;
2017

Abstract

Primary myelofibrosis is characterized by the development of fibrosis in the bone marrow that contributes to ineffective hematopoiesis. Bone marrow fibrosis is the result of a complex and not yet fully understood interaction among megakaryocytes, myeloid cells, fibroblasts, and endothelial cells. Here, we report that >30% of the endothelial cells in the small vessels of the bone marrow and spleen of patients with primary myelofibrosis have a mesenchymal phenotype, which is suggestive of the process known as endothelial-to-mesenchymal transition (EndMT). EndMT can be reproduced in vitro by incubation of cultured endothelial progenitor cells or spleen-derived endothelial cells with inflammatory cytokines. Megakaryocytes appear to be implicated in this process, because EndMT mainly occurs in the microvessels close to these cells, and because megakaryocyte-derived supernatant fluid can reproduce the EndMT switch in vitro. Furthermore, EndMT is an early event in a JAK2-V617F knock-in mouse model of primary myelofibrosis. Overall, these data show for the first time that microvascular endothelial cells in the bone marrow and spleen of patients with primary myelofibrosis show functional and morphologic changes that are associated to the mesenchymal phenotype.
2017
187
1879
1892
Goal 3: Good health and well-being for people
Erba, Benedetta Gaia; Gruppi, Cristian; Corada, Monica; Pisati, Federica; Rosti, Vittorio; Bartalucci, Niccoloâ ; Villeval, Jean-Luc; Vannucchi, Alessandro Maria; Barosi, Giovanni; Balduini, Alessandra; Dejana, Elisabetta
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Utilizza questo identificatore per citare o creare un link a questa risorsa: https://hdl.handle.net/2158/1106658
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