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Am J Hematol. 2018 May;93(5):615-622. doi: 10.1002/ajh.25047. Epub 2018 Feb 8.

The spleen of patients with myelofibrosis harbors defective mesenchymal stromal cells.

Author information

1
Pediatric Onco-Hematology/Cell Factory, IRCCS Policlinico San Matteo Foundation, Pavia, Italy.
2
Department of Molecular Medicine, University of Pavia, Pavia, Italy.
3
Laboratory of Biochemistry, Biotechnology and Advanced Diagnosis, IRCCS Policlinico San Matteo Foundation, Pavia, Italy.
4
Center for the Study of Myelofibrosis, Laboratory of Biochemistry, Biotechnology and Advanced Diagnosis, IRCCS Policlinico San Matteo Foundation, Pavia, Italy.
5
Department of Hematology-Oncology, IRCCS Policlinico San Matteo Foundation, Pavia, Italy.
6
Department of Clinical and Experimental Medicine, Research and Innovation Center for Myeloproliferative Diseases, Azienda Ospedaliera Universitaria Careggi, University of Florence, Florence, Italy.
7
Department of Clinical, Surgical, Diagnostic and Pediatric Sciences, University of Pavia, IRCCS Policlinico San Matteo Foundation, Pavia, Italy.
8
Hematology and Bone Marrow Transplant Unit, Azienda Ospedaliera Papa Giovanni XXIII, Bergamo, Italy.
9
Hematology Division, IRCCS Ca' Granda-Maggiore Policlinico Hospital Foundation, Milan, Italy.

Abstract

Splenic hematopoiesis is a major feature in the course of myelofibrosis (MF). In fact, the spleen of patients with MF contains malignant hematopoietic stem cells retaining a complete differentiation program, suggesting both a pivotal role of the spleen in maintaining the disease and a tight regulation of hematopoiesis by the splenic microenvironment, in particular by mesenchymal stromal cells (MSCs). Little is known about splenic MSCs (Sp-MSCs), both in normal and in pathological context. In this work, we have in vitro expanded and characterized Sp-MSCs from 25 patients with MF and 13 healthy subjects (HS). They shared similar phenotype, growth kinetics, and differentiation capacity. However, MF Sp-MSCs expressed significant lower levels of nestin, and favored megakaryocyte (Mk) differentiation in vitro at a larger extent than their normal counterpart. Moreover, they showed a significant upregulation of matrix metalloprotease 2 (MMP2) and fibronectin 1 (FN1) genes both at mRNA expression and at protein level, and, finally, developed genetic abnormalities which were never detected in HS-derived Sp-MSCs. Our data point toward the existence of a defective splenic niche in patients with MF that could be responsible of some pathological features of the disease, including the increased trafficking of CD34+ cells and the expansion of the megakaryocytic lineage.

PMID:
29359451
DOI:
10.1002/ajh.25047
[Indexed for MEDLINE]
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