Gain of function, loss of control - a molecular basis for chronic myeloproliferative disorders

After years of lack of knowledge concerning the pathogenesis of these conditions, four articles have been published in a period of six weeks (March 19–April 28, 2005) describing a unique gain-of-function mutation of the Janus kinase 2 (JAK2) gene in patients with polycythemia vera, essential thrombocythemia and idiopathic myelofibrosis. This perspective article analyzes the biologic and clinical implications of this mutation. Although the currently available data clearly demonstrate that JAK2 V617F participates in the pathogenesis of myeloproliferative disorders, the mutation’s precise place in the hierarchical order of events remains to be established.