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Platelet derived growth factor receptor-beta (PDGFRβ) expression is limited to activated stromal cells in the bone marrow and shows a strong correlation with the grade of myelofibrosis

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Abstract

Platelet derived growth factor receptor (PDGFR) is a membrane tyrosine-kinase receptor required for fibroblast activation in stromal proliferations. In order to assess the role of PDGFR in myelofibrosis (MF) we determined in 60 bone marrow biopsies the occurrence and distribution of its α and β subunits in normal and fibrotic bone marrow stroma using immunohistochemistry, and compared this with the grade of MF determined by Gömöri’s silver impregnation. PDGF receptor subunits were found to be differentially expressed in the marrow parenchyma. PDGFRα expression identified megakaryocytes, endosteal and endothelial cells while PDGFRβ was virtually absent from inter-trabecular spaces in normal marrow. Activated fibroblasts characteristic for MF intensely expressed PDGFRβ but only a moderate increase in PDGFRα expression was seen. Semi-quantitative PDGFRβ immunoreactivity scores correlated well with the grade of MF in the vast majority of the MF cases (Spearman r= 0.83). Altogether, 21/60 (35.0%) cases showed a relative increase of PDGFRβ expression, compared to the MF grade, suggesting that increased stromal PDGFRβ expression occurs early and precedes reticulin and collagen fiber production during fibroblast activation. In conclusion, bone marrow PDGFRβ expression closely correlates with the grade of MF. Increased immunoreactivity for PDGFRβ occurs already in the prefibrotic stage of the disease and might allow a functional classification of the bone marrow stromal reaction.

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Acknowledgements

The publication and scientific work was supported by the TÁMOP-4.2.2.A-11/1/KOV-2012- 0045 project and the MTA-DE Vascular Biology, Thrombosis and Hemostasis Research Group (vascular biology – 11003) of the Hungarian Academy of Sciences.

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We declare that we have no conflict of interest.

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Authors and Affiliations

  1. Department of Pathology, University of Debrecen, Nagyerdei krt. 98, 4032, Debrecen, Hungary

    Judit Bedekovics, Lívia Beke & Gábor Méhes

  2. Second Department of Internal Medicine, University of Debrecen, Debrecen, Hungary

    Attila Kiss

  3. Department of Pathology, Kenézy Gyula Hospital and Outpatient Clinic, Debrecen, Hungary

    Katalin Károlyi

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  1. Judit Bedekovics
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  2. Attila Kiss
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  3. Lívia Beke
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  4. Katalin Károlyi
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  5. Gábor Méhes
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Correspondence to Gábor Méhes.

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Bedekovics, J., Kiss, A., Beke, L. et al. Platelet derived growth factor receptor-beta (PDGFRβ) expression is limited to activated stromal cells in the bone marrow and shows a strong correlation with the grade of myelofibrosis. Virchows Arch 463, 57–65 (2013). https://doi.org/10.1007/s00428-013-1434-0

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  • DOI: https://doi.org/10.1007/s00428-013-1434-0

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