Experimental therapy in myelofibrosis with myeloid metaplasia

Myelofibrosis with myeloid metaplasia (MMM) is a Philadelphia chromosome-negative myeloproliferative disorder that is characterised by constitutional symptoms, progressive anaemia and extramedullary haematopoiesis. There are no curative therapies available for patients with MMM apart from stem cell transplantation, which is associated with significant morbidity and mortality, and for which most patients are not suitable candidates. Traditional pharmacological therapy of MMM has focused on the palliation of symptoms associated with myeloproliferation and correction of cytopoenias. Recently, new findings regarding the molecular basis of MMM and the pathogenesis of the associated bone marrow stromal reaction have provided both basic and clinical researchers with invaluable tools to develop effective targeted therapies for patients with MMM. Several novel treatment strategies are being investigated including antiangiogenic agents, signal transduction inhibitors, inhibitors of fibrogenesis and small-molecule inhibitors of the JAK2^V617F mutation. This article reviews the current status of experimental novel therapies for MMM.