Pathogenesis of Idiopathic Myelofibrosis: A Review

During the last two decades, important progress has been made in the understanding of the nature and pathogenesis of idiopathic myelofibrosis. The characteristic extracellular matrix is composed of a variety of interstitial and basement membrane glycoproteins, including collagen types I, III, IV, V and VI, fibronectin, vitronectin, laminin and tenascin, and a marked neovascularisation. In contrast to the clonal haematopoiesis, the increased stromal tissue is a reactive, or secondary phenomenon, resulting from the inappropriate release of megakaryocyte/platelet-derived growth factors, including PDGF, TGF-β, bFGF and calmodulin. Recent cytogenetic studies have highlighted three chromosomal abnormalities, namely del(13q), del(20q) and partial trisomy 1q, that account for 70% of all abnormalities at diagnosis, and suggests that in many patients gene loss and/or inactivation may be an important pathogenetic mechanism.