Neuropilin2 in Mesenchymal Stromal Cells as a Potential Novel Therapeutic Target in Myelofibrosis.

Autor: Vosbeck K; Institute for Pathology, University Hospital Bonn, 53127 Bonn, Germany., Förster S; Institute for Pathology, University Hospital Bonn, 53127 Bonn, Germany., Mayr T; Institute for Pathology, University Hospital Bonn, 53127 Bonn, Germany., Sahu A; Institute for Medical Biometry, Informatics and Epidemiology, Medical Faculty, University of Bonn, 53127 Bonn, Germany., Haddouti EM; Department of Orthopedics and Trauma Surgery, University Hospital Bonn, 53127 Bonn, Germany., Al-Adilee O; Institute for Pathology, University Hospital Bonn, 53127 Bonn, Germany., Körber RM; Department of Medicine III, University Hospital Bonn, 53127 Bonn, Germany., Bisht S; Department of Medicine III, University Hospital Bonn, 53127 Bonn, Germany., Muders MH; Institute for Pathology, University Hospital Bonn, 53127 Bonn, Germany., Nesic S; Core Unit for Bioinformatics Data Analysis, Medical Faculty, University of Bonn, Venusberg-Campus 1, 53127 Bonn, Germany., Buness A; Core Unit for Bioinformatics Data Analysis, Medical Faculty, University of Bonn, Venusberg-Campus 1, 53127 Bonn, Germany., Kristiansen G; Institute for Pathology, University Hospital Bonn, 53127 Bonn, Germany., Schildberg FA; Department of Orthopedics and Trauma Surgery, University Hospital Bonn, 53127 Bonn, Germany., Gütgemann I; Institute for Pathology, University Hospital Bonn, 53127 Bonn, Germany.
Jazyk: angličtina
Zdroj: Cancers [Cancers (Basel)] 2024 May 18; Vol. 16 (10). Date of Electronic Publication: 2024 May 18.
DOI: 10.3390/cancers16101924
Abstrakt: Bone marrow fibrosis in myeloproliferative neoplasm (MPN), myelodysplastic syndromes (MDS), MPN/MDS overlap syndromes and acute myeloid leukemia (AML) is associated with poor prognosis and early treatment failure. Myelofibrosis (MF) is accompanied by reprogramming of multipotent bone marrow mesenchymal stromal cells (MSC) into osteoid and fiber-producing stromal cells. We demonstrate NRP2 and osteolineage marker NCAM1 (neural cell adhesion molecule 1) expression within the endosteal niche in normal bone marrow and aberrantly in MPN, MDS MPN/MDS overlap syndromes and AML ( n = 99), as assessed by immunohistochemistry. Increased and diffuse expression in mesenchymal stromal cells and osteoblasts correlates with high MF grade in MPN ( p < 0.05 for NRP2 and NCAM1). Single cell RNA sequencing (scRNAseq) re-analysis demonstrated NRP2 expression in endothelial cells and partial co-expression of NRP2 and NCAM1 in normal MSC and osteoblasts. Potential ligands included transforming growth factor β1 (TGFB1) from osteoblasts and megakaryocytes. Murine ThPO and JAK2 V617F myelofibrosis models showed co-expression of Nrp2 and Ncam1 in osteolineage cells, while fibrosis-promoting MSC only express Nrp2. In vitro experiments with MC3T3-E1 pre-osteoblasts and analysis of Nrp2 - / - mouse femurs suggest that Nrp2 is functionally involved in osteogenesis. In summary, NRP2 represents a potential novel druggable target in patients with myelofibrosis.
Databáze: MEDLINE
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