title: Activated fibronectin-secretory phenotype of mesenchymal stromal cells in pre-fibrotic myeloproliferative neoplasms.
abstract: We characterized bone marrow stromal cells (BMSC) from patients with pre-fibrotic myeloproliferative neoplasms (MPN). MPN-BMSC showed decreased capacity to stimulate the proliferation of colony-forming units of normal hematopoietic stem and progenitor cells and displayed increased matrix remodelling (in particular fibronectin deposition) compared to control BMSC. This finding was confirmed in pre-fibrotic MPN bone marrow biopsies in a tissue microarray (n = 34), which stained positive for fibronectin in the absence of reticulin as a standard myelofibrosis marker. Fibronectin expression correlated significantly with reduced haemoglobin levels in MPN-patients (p = 0.007; R2 = 0.42). Our data show significant cell-intrinsic alterations in MPN-MSC and suggest that Fibronectin expression might be applicable as a biomarker for the identification of early myelofibrotic transformation in reticulin-negative MPN.
authors.affiliation: Division of Hematology, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, 1 Blackfan Circle, Boston, MA, 02115, USA. reschneider@ukaachen.de.|Institute of Pathology, University Hospital Aachen, RWTH Aachen University, Pauwelsstrasse 30, Aachen, 52074, Germany. reschneider@ukaachen.de.
authors.forename: Rebekka K
authors.initials: RK
authors.lastname: Schneider
authors.affiliation: Department of Oncology, Hematology and Stem cell transplantation, University Hospital Aachen, RWTH Aachen University, Pauwelsstrasse 30, Aachen, 52074, Germany. sziegler@ukaachen.de.
authors.forename: Susanne
authors.initials: S
authors.lastname: Ziegler
authors.affiliation: Institute of Pathology, University Hospital Aachen, RWTH Aachen University, Pauwelsstrasse 30, Aachen, 52074, Germany. isabelle.leisten@rwth-aachen.de.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Leisten
authors.affiliation: Institute of Pathology, University Hospital Aachen, RWTH Aachen University, Pauwelsstrasse 30, Aachen, 52074, Germany. mventuraferreira@ukaachen.de.|Department of Oncology, Hematology and Stem cell transplantation, University Hospital Aachen, RWTH Aachen University, Pauwelsstrasse 30, Aachen, 52074, Germany. mventuraferreira@ukaachen.de.
authors.forename: Monica S V
authors.initials: MS
authors.lastname: Ferreira
authors.affiliation: Department of Oncology, Hematology and Stem cell transplantation, University Hospital Aachen, RWTH Aachen University, Pauwelsstrasse 30, Aachen, 52074, Germany. anne-2704@web.de.
authors.forename: Anne
authors.initials: A
authors.lastname: Schumacher
authors.affiliation: Department of Orthopaedic Surgery, University Hospital Aachen, RWTH Aachen University, Pauwelsstrasse 30, Aachen, 52074, Germany. brath@ukaachen.de.
authors.forename: Björn
authors.initials: B
authors.lastname: Rath
authors.affiliation: Department of Biochemistry and Molecular Biology, University Hospital Aachen, RWTH Aachen University, Pauwelsstrasse 30, Aachen, 52074, Germany. dirk.fahrenkamp@rwth-aachen.de.
authors.forename: Dirk
authors.initials: D
authors.lastname: Fahrenkamp
authors.affiliation: Department of Biochemistry and Molecular Biology, University Hospital Aachen, RWTH Aachen University, Pauwelsstrasse 30, Aachen, 52074, Germany. mueller-newen@rwth-aachen.de.
authors.forename: Gerhard
authors.initials: G
authors.lastname: Müller-Newen
authors.affiliation: Department of Oncology, Hematology and Stem cell transplantation, University Hospital Aachen, RWTH Aachen University, Pauwelsstrasse 30, Aachen, 52074, Germany. mcrysandt@ukaachen.de.
authors.forename: Martina
authors.initials: M
authors.lastname: Crysandt
authors.affiliation: Department of Oncology, Hematology and Stem cell transplantation, University Hospital Aachen, RWTH Aachen University, Pauwelsstrasse 30, Aachen, 52074, Germany. swilop@ukaachen.de.
authors.forename: Stefan
authors.initials: S
authors.lastname: Wilop
authors.affiliation: Department of Oncology, Hematology and Stem cell transplantation, University Hospital Aachen, RWTH Aachen University, Pauwelsstrasse 30, Aachen, 52074, Germany. ejost@ukaachen.de.
authors.forename: Edgar
authors.initials: E
authors.lastname: Jost
authors.affiliation: Department of Oncology, Hematology and Stem cell transplantation, University Hospital Aachen, RWTH Aachen University, Pauwelsstrasse 30, Aachen, 52074, Germany. skoschmieder@kaachen.de.
authors.forename: Steffen
authors.initials: S
authors.lastname: Koschmieder
authors.affiliation: Institute of Pathology, University Hospital Aachen, RWTH Aachen University, Pauwelsstrasse 30, Aachen, 52074, Germany. rknuechel-clarke@ukaachen.de.
authors.forename: Ruth
authors.initials: R
authors.lastname: Knüchel
authors.affiliation: Department of Oncology, Hematology and Stem cell transplantation, University Hospital Aachen, RWTH Aachen University, Pauwelsstrasse 30, Aachen, 52074, Germany. tbruemmendorf@ukaachen.de.
authors.forename: Tim H
authors.initials: TH
authors.lastname: Brümmendorf
authors.affiliation: Department of Oncology, Hematology and Stem cell transplantation, University Hospital Aachen, RWTH Aachen University, Pauwelsstrasse 30, Aachen, 52074, Germany. pziegler@ukaachen.de.
authors.forename: Patrick
authors.initials: P
authors.lastname: Ziegler
mesh_terms: D005353:Fibronectins / Q000378:metabolism*; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000378:metabolism / Q000473:pathology*; D009196:Myeloproliferative Disorders / Q000235:genetics / Q000473:pathology*; D010641:Phenotype; D046888:Tissue Array Analysis
chemical_list: D005353:Fibronectins