JAKing up hematopoietic proliferation.
Mutations that deregulate proliferation and survival pathways have emerged as a common molecular theme in the pathogenesis of myeloproliferative disorders (MPDs). Three studies now report an amino acid substitution in the JAK2 kinase in most patients with polycythemia vera as well as in some cases of essential thrombocythemia and chronic idiopathic myelofibrosis. Functional analysis demonstrates that this mutation confers erythropoietin-independent growth in vitro, deregulates signaling pathways downstream of JAK2, and causes polycythemia in mice. These results open new avenues for diagnosing and classifying patients with these disorders, and identify a new molecular target for drug discovery.
Shannon
Kevin
K
Department of Pediatrics and Comprehensive Cancer Center, University of California, San Francisco, California 94143, USA. kevins@itsa.ucsf.edu
Van Etten
Richard A
RA
D000818:Animals; D004920:Erythropoiesis / Q000235:genetics; D006801:Humans; D053614:Janus Kinase 2; D051379:Mice; D008954:Models, Biological; D009154:Mutation / Q000235:genetics*; D009196:Myeloproliferative Disorders / Q000235:genetics*; D011086:Polycythemia / Q000235:genetics; D011087:Polycythemia Vera / Q000235:genetics; D055728:Primary Myelofibrosis / Q000235:genetics; D011505:Protein-Tyrosine Kinases / Q000235:genetics*; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D015398:Signal Transduction / Q000235:genetics; D013920:Thrombocythemia, Essential / Q000235:genetics
D011518:Proto-Oncogene Proteins; D011505:Protein-Tyrosine Kinases; C507924:JAK2 protein, human; C507926:Jak2 protein, mouse; D053614:Janus Kinase 2