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

Judit Bedekovics, Attila Kiss, Lívia Beke, Katalin Károlyi, G. Méhes

Research output: Contribution to journalArticle

11 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)57-65
Number of pages9
JournalVirchows Archiv
Volume463
Issue number1
DOIs
Publication statusPublished - Jul 2013

Fingerprint

Platelet-Derived Growth Factor beta Receptor
Primary Myelofibrosis
Mesenchymal Stromal Cells
Bone Marrow
Platelet-Derived Growth Factor Receptors
Fibroblasts
Reticulin
Megakaryocytes
Receptor Protein-Tyrosine Kinases
Silver
Collagen
Endothelial Cells
Immunohistochemistry

Keywords

  • Bone marrow
  • Myelofibrosis
  • PDGFR
  • Stromal activation

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Cell Biology
  • Molecular Biology

Cite this

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. / Bedekovics, Judit; Kiss, Attila; Beke, Lívia; Károlyi, Katalin; Méhes, G.

In: Virchows Archiv, Vol. 463, No. 1, 07.2013, p. 57-65.

Research output: Contribution to journalArticle

@article{420130d240fa4194aab476c51c0449a8,
title = "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",
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 G{\"o}m{\"o}ri'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.",
keywords = "Bone marrow, Myelofibrosis, PDGFR, Stromal activation",
author = "Judit Bedekovics and Attila Kiss and L{\'i}via Beke and Katalin K{\'a}rolyi and G. M{\'e}hes",
year = "2013",
month = "7",
doi = "10.1007/s00428-013-1434-0",
language = "English",
volume = "463",
pages = "57--65",
journal = "Virchows Archiv - A Pathological Anatomy and Histopathology",
issn = "0945-6317",
publisher = "Springer Verlag",
number = "1",

}

TY - JOUR

T1 - 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

AU - Bedekovics, Judit

AU - Kiss, Attila

AU - Beke, Lívia

AU - Károlyi, Katalin

AU - Méhes, G.

PY - 2013/7

Y1 - 2013/7

N2 - 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.

AB - 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.

KW - Bone marrow

KW - Myelofibrosis

KW - PDGFR

KW - Stromal activation

UR - http://www.scopus.com/inward/record.url?scp=84879836183&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84879836183&partnerID=8YFLogxK

U2 - 10.1007/s00428-013-1434-0

DO - 10.1007/s00428-013-1434-0

M3 - Article

VL - 463

SP - 57

EP - 65

JO - Virchows Archiv - A Pathological Anatomy and Histopathology

JF - Virchows Archiv - A Pathological Anatomy and Histopathology

SN - 0945-6317

IS - 1

ER -