{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,31]],"date-time":"2026-03-31T18:07:26Z","timestamp":1774980446406,"version":"3.50.1"},"reference-count":31,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2023,3,14]],"date-time":"2023-03-14T00:00:00Z","timestamp":1678752000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["European J of Haematology"],"published-print":{"date-parts":[[2023,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Essential thrombocythemia (ET) cases without canonical <jats:italic>JAK2<\/jats:italic>, <jats:italic>CALR<\/jats:italic>, or <jats:italic>MPL<\/jats:italic> mutations, that is, triple\u2010negative (TN) ET, have been found in 10%\u201320% of ET cases. Owing to the limited number of TN ET cases, its clinical significance remains unclear. This study evaluated TN ET's clinical characteristics and identified novel driver mutations. Among 119 patients with ET, 20 (16.8%) had no canonical <jats:italic>JAK2\/CALR\/MPL<\/jats:italic> mutations. Patients with TN ET tended to be younger and had lower white blood cell counts and lactate dehydrogenase values. We identified putative driver mutations in 7 (35%): <jats:italic>MPL<\/jats:italic> S204P, <jats:italic>MPL<\/jats:italic> L265F, <jats:italic>JAK2<\/jats:italic> R683G, and <jats:italic>JAK2<\/jats:italic> T875N were previously reported as candidate driver mutations in ET. Moreover, we identified a <jats:italic>THPO<\/jats:italic> splicing site mutation, <jats:italic>MPL<\/jats:italic>*636Wext*12, and <jats:italic>MPL<\/jats:italic> E237K. Four of the seven identified driver mutations were germline. Functional studies on <jats:italic>MPL<\/jats:italic>*636Wext*12 and <jats:italic>MPL<\/jats:italic> E237K revealed that they are gain\u2010of\u2010function mutants that increase MPL signaling and confer thrombopoietin hypersensitivity with very low efficiency. Patients with TN ET tended to be younger, although this was thought to be due to the inclusion of germline mutations, hereditary thrombocytosis. Accumulating the genetic and clinical characteristics of noncanonical mutations may help future clinical interventions in TN ET and hereditary thrombocytosis.<\/jats:p>","DOI":"10.1111\/ejh.13945","type":"journal-article","created":{"date-parts":[[2023,2,22]],"date-time":"2023-02-22T10:49:26Z","timestamp":1677062966000},"page":"639-647","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Identification of putative noncanonical driver mutations in patients with essential thrombocythemia"],"prefix":"10.1111","volume":"110","author":[{"given":"Akihiko","family":"Arai","sequence":"first","affiliation":[{"name":"Department of Hematology and Rheumatology Graduate School of Medical and Dental Sciences, Kagoshima University  Kagoshima Japan"},{"name":"Department of Hematology and Rheumatology Kagoshima City Hospital  Kagoshima 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