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• W2109558519 abstract "In 1951, William Dameshek speculated on the common origin of the chronic myeloproliferative disorders--polycythemia vera (PV), essential thrombocythemia (ET), chronic idiopathic myelofibrosis (IMF), and chronic myelogenous leukemia (CML). Subsequent work suggested that all arose from the hematopoietic stem cell. About 20 years ago the oncogene responsible for CML, bcr-abl, was identified, and more recently the mutant genes that cause hypereosinophilic syndrome and systemic mast cell disorder have been discovered. However, until very recently, the origin of PV, ET, and IMF have defied molecular explanation. In 2005, four separate groups working on tyrosine kinase signal transduction reported a gain-of-function, valine-to-phenyalanine, mutation at position 617 in the JH2 domain of the Janus kinase (JAK) 2 cytoplasmic tyrosine kinase. This mutation requires the presence of the erythropoietin, thrombopoietin, or granulocyte-colony stimulating factor receptor/s for function, the mutation leads to functional hyperactivity and appears responsible for hematopoietic growth factor hypersensitivity, the most characteristic finding in these disorders. Virtually all patients with PV and substantial proportions of those with ET and IMF have now been shown to harbor this mutation. The mutant kinase appears to be a useful diagnostic test for myeloproliferative disorders and may have prognostic value. Future research will undoubtedly focus on the development of specific inhibitors as therapeutic agents as well as answering a number of questions that remain regarding the role of signal intensity, genotypic and phenotypic expression and the possible involvement of additional as yet unidentified mutations in these disorders." @default.
• W2109558519 created "2016-06-24" @default.
• W2109558519 creator A5008851883 @default.
• W2109558519 date "2007-03-01" @default.
• W2109558519 modified "2023-09-23" @default.
• W2109558519 title "The chronic myeloproliferative disorders and mutation of JAK2: Dameshek's 54 year old speculation comes of age" @default.
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• W2109558519 doi "https://doi.org/10.1016/j.beha.2006.11.005" @default.
• W2109558519 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/2684109" @default.
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