title: A JAK2 mutation in myeloproliferative disorders: pathogenesis and therapeutic and scientific prospects.
abstract: Myeloproliferative disorders include several pathologies sharing the common feature of being clonal hematopoietic stem cell diseases. The molecular basis of chronic myeloid leukemia was characterized many years ago with the discovery of the t(9;22) translocation and its product the BCR-ABL oncoprotein. The recent finding of a recurrent mutation in the Janus 2 tyrosine kinase gene is a major advance in our understanding of the pathogenesis of several other myeloproliferative disorders, including polycythemia vera, essential thrombocythemia and idiopathic myelofibrosis. Although this work clearly identifies a frequent ( approximately 50%) subgroup of myeloproliferative disorders and explains most biological abnormalities described so far, it also raises the major question of how a single mutation can explain disease heterogeneity. Such a recurrent and unique mutation leading to a tyrosine kinase deregulation would make a suitable target for the development of specific therapies.
authors.affiliation: INSERM U362, Institut Gustave Roussy, Paris XI University, PR1, 39 rue Camille Desmoulins, 94805 Villejuif Cedex, France. chloe.james@wanadoo.fr
authors.forename: Chloé
authors.initials: C
authors.lastname: James
authors.forename: Valérie
authors.initials: V
authors.lastname: Ugo
authors.forename: Nicole
authors.initials: N
authors.lastname: Casadevall
authors.forename: Stefan N
authors.initials: SN
authors.lastname: Constantinescu
authors.forename: William
authors.initials: W
authors.lastname: Vainchenker
mesh_terms: D040461:Gene Components; D006801:Humans; D053614:Janus Kinase 2; D020125:Mutation, Missense / Q000235:genetics*; D009196:Myeloproliferative Disorders / Q000235:genetics* / Q000473:pathology* / Q000628:therapy; D011505:Protein-Tyrosine Kinases / Q000235:genetics*; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D017467:Receptors, Erythropoietin / Q000378:metabolism; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology*
chemical_list: D011518:Proto-Oncogene Proteins; D017467:Receptors, Erythropoietin; D011505:Protein-Tyrosine Kinases; C507924:JAK2 protein, human; D053614:Janus Kinase 2