{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T04:21:19Z","timestamp":1789014079566,"version":"build-2803163510"},"reference-count":19,"publisher":"Wiley","issue":"3-4","license":[{"start":{"date-parts":[[2005,11,14]],"date-time":"2005-11-14T00:00:00Z","timestamp":1131926400000},"content-version":"vor","delay-in-days":74,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Hematological Oncology"],"published-print":{"date-parts":[[2005,9]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The discovery this year of a single mutation in the Janus Kinase (<jats:italic>JAK<\/jats:italic>)\u20102 gene in a high percentage of cases of polycythaemia vera (PV), essential thrombocythaemia (ET) and myelofibrosis suggests that it maybe the underlying molecular mechanism for these disorders. Different approaches from the inhibition of the tyrosine kinase JAK2, widespread search for mutations in tyrosine kinases, and investigation of the short arm of chromosome 9 where <jats:italic>JAK2<\/jats:italic> is located all led to the discovery of the V617F JAK2 mutation. Substitution of a valine for a phenylalanine destabilizes the JH2 domain of JAK2 causes loss of the auto\u2010inhibitory activity of this domain and explains some of the biological phenomena observed in patients with myeloproliferative disorders (MPD). The V617F JAK2 mutation can be detected by PCR\u2010direct sequencing using DNA from the granulocyte lineage or with increased sensitivity by the amplification refractory mutation system using DNA from unfractionated blood. Pyrosequencing assays can be used to quantitate allele ratios to accurately define homozygote and heterozygote status. This single mutation is widespread having been detected in related MPD and other haematological malignancies. This leads to a number of further questions about the role of this single mutation in the clinical pattern of disease. Copyright \u00a9 2005 John Wiley &amp; Sons, Ltd.<\/jats:p>","DOI":"10.1002\/hon.761","type":"journal-article","created":{"date-parts":[[2005,11,16]],"date-time":"2005-11-16T23:19:51Z","timestamp":1132183191000},"page":"91-93","source":"Crossref","is-referenced-by-count":35,"title":["The V617F JAK2 mutation and the myeloproliferative disorders"],"prefix":"10.1002","volume":"23","author":[{"given":"Melanie J","family":"Percy","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mary Frances","family":"McMullin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2005,11,14]]},"reference":[{"key":"e_1_2_1_2_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V6.4.372.372"},{"key":"e_1_2_1_3_2","first-page":"1","article-title":"A unique clonal JAK2 mutation leading to constitutive signaling causes polycythaemia vera","volume":"3546","author":"James C","year":"2005","journal-title":"Nature"},{"key":"e_1_2_1_4_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa051113"},{"key":"e_1_2_1_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccr.2005.03.023"},{"key":"e_1_2_1_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(05)71142-9"},{"key":"e_1_2_1_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.exphem.2003.11.003"},{"key":"e_1_2_1_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0301-472X(01)00789-5"},{"key":"e_1_2_1_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(05)71142-9"},{"key":"e_1_2_1_10_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM197406132902419"},{"key":"e_1_2_1_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0301-472X(01)00637-3"},{"key":"e_1_2_1_12_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199802263380902"},{"key":"e_1_2_1_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.exphem.2004.10.017"},{"key":"e_1_2_1_14_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2005-03-1320"},{"key":"e_1_2_1_15_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2005-03-1183"},{"key":"e_1_2_1_16_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.C500138200"},{"key":"e_1_2_1_17_2","article-title":"Altered gene expression in myeloproliferative disorders correlates with activation of signaling by the V617F mutation of JAK2","author":"Kravolics R","year":"2005","journal-title":"Blood"},{"key":"e_1_2_1_18_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2005-04-1515"},{"key":"e_1_2_1_19_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2005-05-1800"},{"key":"e_1_2_1_20_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2005-05-1898"}],"container-title":["Hematological Oncology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fhon.761","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/hon.761","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,31]],"date-time":"2023-08-31T16:43:50Z","timestamp":1693500230000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/hon.761"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2005,9]]},"references-count":19,"journal-issue":{"issue":"3-4","published-print":{"date-parts":[[2005,9]]}},"alternative-id":["10.1002\/hon.761"],"URL":"https:\/\/doi.org\/10.1002\/hon.761","archive":["Portico"],"relation":{},"ISSN":["0278-0232","1099-1069"],"issn-type":[{"value":"0278-0232","type":"print"},{"value":"1099-1069","type":"electronic"}],"subject":[],"published":{"date-parts":[[2005,9]]}}}