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Activated fibronectin-secretory phenotype of mesenchymal stromal cells in pre-fibrotic myeloproliferative neoplasms
Authors:Email author" target="_blank">Rebekka?K?SchneiderEmail author  Susanne?Ziegler  Isabelle?Leisten  Monica?SV?Ferreira  Anne?Schumacher  Bj?rn?Rath  Dirk?Fahrenkamp  Gerhard?Müller-Newen  Martina?Crysandt  Stefan?Wilop  Edgar?Jost  Steffen?Koschmieder  Ruth?Knüchel  Tim?H?Brümmendorf  Patrick?Ziegler
Institution:1.Division of Hematology, Department of Medicine,Brigham and Women’s Hospital, Harvard Medical School,Boston,USA;2.Institute of Pathology,University Hospital Aachen, RWTH Aachen University,Aachen,Germany;3.Department of Oncology, Hematology and Stem cell transplantation,University Hospital Aachen, RWTH Aachen University,Aachen,Germany;4.Department of Orthopaedic Surgery,University Hospital Aachen, RWTH Aachen University,Aachen,Germany;5.Department of Biochemistry and Molecular Biology,University Hospital Aachen, RWTH Aachen University,Aachen,Germany
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.
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