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

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 beta (TGF-beta), platelet-derived growth factor (PDGF), vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF) and corresponding receptors. Staining distribution and intensity for TGF-beta, PDGF, VEGF, TGF-beta 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-beta type I receptor (TGF-betaRI) 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-betaRI upregulation and bFGF overexpression by megakaryocytes may cause bone marrow microenvironmental changes in MMM patients.