The JAK2(V617F) tyrosine kinase mutation in myeloproliferative disorders: Summary of published literature and a perspective.
A common somatic point mutation has recently been identified in the Janus kinase 2 (JAK2) gene in virtually all cases of polycythemia vera and in a majority of patients with essential thrombocythemia and idiopathic myelofibrosis. This common mutation in the pseudokinase autoinhibitory domain of the enzyme results in constitutive tyrosine kinase activation, which in turn leads to cytokine hypersensitivity and factor independence in factor-dependent cell lines, and causes polycythemia in mice. This discovery has led to greater understanding of the molecular pathogenesis of the chronic myeloproliferative disorders, which may translate into targeted therapy.
Wadleigh
Martha
M
Dana Farber Cancer Institute, Boston, MA 02115, USA. mwadleigh@partners.org
Gilliland
D Gary
DG
D019943:Amino Acid Substitution; D000818:Animals; D002384:Catalysis; D019070:Cell Lineage; D002999:Clone Cells / Q000201:enzymology; D004789:Enzyme Activation; D006801:Humans; D053614:Janus Kinase 2 / Q000737:chemistry / Q000235:genetics* / Q000502:physiology; D051379:Mice; D020125:Mutation, Missense; D022423:Myeloid Cells / Q000201:enzymology; D009196:Myeloproliferative Disorders / Q000201:enzymology* / Q000209:etiology / Q000235:genetics; D010641:Phenotype; D017354:Point Mutation; D011487:Protein Conformation; D015398:Signal Transduction
C507924:JAK2 protein, human; C507926:Jak2 protein, mouse; D053614:Janus Kinase 2