The chronic myeloproliferative diseases, Polycythemia Vera (PV), Essential Thrombocythemia (ET), Idiopathic Myelofibrosis (IMF) and Chronic Myelogenous Leukemia (CML) represent a spectrum of pathogenetically related disorders of varying clinical manifestations. While the origin of CML has been traced to a dysregulated protein kinase, the product of the bcr/abl oncogene, the molecular basis of PV, ET and IMF, which as a group share more similarities with each other than with CML, has been more recalcitrant to solution. However, a major insight into the molecular basis for the enhanced myeloproliferation and clonal dominance that characterizes these disorders is now upon us; four groups of investigators have recently reported that a single, somatic mutation in the protein tyrosine kinase JAK2 appears responsible for many of the features of PV, ET and IMF, an observation that promises to impact the diagnosis and treatment of patients with these disorders, and to spur additional research into the origins of dysregulated cell growth and function.
 


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