Pathogenesis of idiopathic myelofibrosis: role of growth factors.

Introduction Idiopathic myelofibrosis, or agnogenic myeloid metaplasia, is a chronic myeloproliferative disorder that is characterised by marrow fibrosis and extramedullary haematopoiesis. The origin of the disease remains an enigma and a source of confusion in management, not least because until recently no meaningful progress had been made regarding its pathophysiology. Research during the past decade in three interrelated areas may offer some hope for the future. First, it is now accepted that the fibroblast proliferation is a reactive, or secondary process and is not, as previously thought, a component of the underlying clonal haematopoiesis. Second, the nature and composition of both normal and myelofibrotic bone marrow stroma has largely been elucidated, and lastly, the pivotal role of inappropriate growth factor release from megakaryocytes as mediators of fibrogenesis has been recognised. This article aims to review the current understanding of the disease's pathogenesis, with particular emphasis on the part played by growth factors.