Dameshek Smiles: Molecular Clues to the Chronic Myeloproliferative Disorders Unmasked

The classic chronic myeloproliferative disorders (MPDs) polycythemia vera (PV), essential thrombocythemia (ET), and idiopathic myelofibrosis (MF) have been historically grouped together because of their overlapping clinical phenotypes. The recent discovery of a single acquired point mutation (V617F) in the Janus kinase 2 (JAK2) gene in most patients with PV and about half of ET and MF patients provides a new starting point for exploring the genetic and biologic mechanisms of disease pathogenesis in these related disorders. This chapter highlights the different roads of discovery to the JAK2 V617F mutation, both in vitro and in vivo experimental data relevant to the mutant JAK2 tyrosine kinase, and new questions raised by the discovery.