Bone marrow immunohistochemical studies of angiogenic cytokines and their receptors in myelofibrosis with myeloid metaplasia

Received 5 August 2002; received in revised form 7 October 2002; accepted 11 October 2002.

Abstract

Bone marrow specimens from 11 patients with myelofibrosis with myeloid metaplasia (MMM) and seven normal controls were studied immunohistochemically to determine expression of transforming growth factor β (TGF-β), platelet-derived growth factor (PDGF), vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF) and corresponding receptors. Staining distribution and intensity for TGF-β, PDGF, VEGF, TGF-β type II receptor, a receptor for PDGF, and receptors for VEGF and bFGF were similar in patients and controls. Bone marrow from 10 MMM patients showed increased TGF-β type I receptor (TGF-βRI) expression in small vessel endothelial cells. Eight patient specimens had bFGF overexpression in megakaryocytes. Increased microvessel density and decreased concentration of bFGF-staining stromal cells accompanied these changes. Microvascular TGF-βRI upregulation and bFGF overexpression by megakaryocytes may cause bone marrow microenvironmental changes in MMM patients.

Abbreviations: ALK, activin receptorlike kinase, bFGF, basic fibroblast growth factor, FGF, fibroblast growth factor, FGFR, fibroblast growth factor receptor, FGFR1, FGFR2, fibroblast growth factor receptor types 1 and 2, MMM, myelofibrosis with myeloid metaplasia, PDGF, platelet-derived growth factor, PDGF-A, PDGF-B, platelet-derived growth factor chains A and B, PDGFR, platelet-derived growth factor receptor, TGF-β, transforming growth factor β, TGF-β1, TGF-β2, TGF-β3, transforming growth factor β isoforms 1, 2, and 3, TGF-βRI, transforming growth factor β type I receptor, TGF-βRII, transforming growth factor β type II receptor, TNF-α, tumor necrosis factor α, VEGF, vascular endothelial growth factor, VEGFR, vascular endothelial growth factor receptor, VEGFR1, VEGFR2, vascular endothelial growth factor types 1 and 2

Keywords: Basic fibroblast growth factor, Bone marrow, Cytokine, Immunohistochemistry, Myelofibrosis, Platelet-derived growth factor, Transforming growth factor, Vascular endothelial growth factor

a Division of Hematopathology, Department of Pathology, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan, ROC

b Division of Hematopathology, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, USA

c Division of Hematology and Internal Medicine, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, USA

Corresponding author.

PII: S0145-2126(02)00268-0

doi:10.1016/S0145-2126(02)00268-0

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