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

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 alpha and beta subunits in normal and fibrotic bone marrow stroma using immunohistochemistry, and compared this with the grade of MF determined by Gomori's silver impregnation. PDGF receptor subunits were found to be differentially expressed in the marrow parenchyma. PDGFR alpha expression identified megakaryocytes, endosteal and endothelial cells while PDGFR beta was virtually absent from inter-trabecular spaces in normal marrow. Activated fibroblasts characteristic for MF intensely expressed PDGFR beta but only a moderate increase in PDGFR alpha expression was seen. Semi-quantitative PDGFR beta 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 PDGFR beta expression, compared to the MF grade, suggesting that increased stromal PDGFR beta expression occurs early and precedes reticulin and collagen fiber production during fibroblast activation. In conclusion, bone marrow PDGFR beta expression closely correlates with the grade of MF. Increased immunoreactivity for PDGFR beta occurs already in the prefibrotic stage of the disease and might allow a functional classification of the bone marrow stromal reaction.