Format

Send to

Choose Destination
Am J Pathol. 2017 Aug;187(8):1879-1892. doi: 10.1016/j.ajpath.2017.04.006.

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

Author information

1
Vascular Biology Laboratory, The FIRC Institute of Molecular Oncology (IFOM) Foundation, Milan, Italy.
2
Department of Molecular Medicine, University of Pavia, Pavia, Italy.
3
Vascular Biology Laboratory, The FIRC Institute of Molecular Oncology (IFOM) Foundation, Milan, Italy; Hystopatology Unit, Cogentech, Milan, Italy.
4
Centre for the Study and Treatment of Myelofibrosis, Biotechnology Research Laboratories, Center for the Study of Myelofibrosis, Istituto di Ricovero e Cura a Carattere Scientifico, Policlinico San Matteo Foundation, Pavia, Italy.
5
Section of Haematology, Department of Medical and Surgical Care, University of Florence, Florence, Italy.
6
INSERM, U1009, Institut Gustave Roussy and Université Paris XI, Villejuif, France.
7
Vascular Biology Laboratory, The FIRC Institute of Molecular Oncology (IFOM) Foundation, Milan, Italy; Department of Immunology, Genetics and Pathology, University of Uppsala, Uppsala, Sweden. Electronic address: elisabetta.dejana@ifom.eu.

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.

PMID:
28728747
DOI:
10.1016/j.ajpath.2017.04.006
[Indexed for MEDLINE]
Free full text

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center