{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T11:59:57Z","timestamp":1792670397741,"version":"4.5.0"},"reference-count":55,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2019,12,27]],"date-time":"2019-12-27T00:00:00Z","timestamp":1577404800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2019,12,27]],"date-time":"2019-12-27T00:00:00Z","timestamp":1577404800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Suspicion of myeloproliferative neoplasms (MPNs) and especially essential thrombocythemia (ET) in primary care is often based solely on blood counts, with patients referred to a haematologist without a thorough evaluation. We retrospectively assessed the role of calreticulin gene (<jats:italic>CALR<\/jats:italic>) mutations in the diagnosis of MPN in this population. We studied <jats:italic>CALR<\/jats:italic> mutations in 524 <jats:italic>JAK2<\/jats:italic> V617F-negative patients with suspected MPN. Uncommon <jats:italic>CALR<\/jats:italic> mutations were confirmed by Sanger sequencing and searched for in the COSMIC or HGMD database. Mutations were defined as frameshift or non-frameshift mutations. <jats:italic>CALR<\/jats:italic> mutations were detected in 23 patients (23\/524\u2009=\u20094.4%). Four mutations detected in our study were newly identified mutations. Non-frameshift mutations were detected in two patients. Most patients (380\/524\u2009=\u200972.5%) were diagnosed with secondary conditions leading to blood count abnormalities such as iron deficiency, inflammatory and infectious diseases, malignancy and hyposplenism. Nine patients (9\/23\u2009=\u200939%) were retrospectively diagnosed with ET based on <jats:italic>CALR<\/jats:italic> mutation confirmation. Two patients with non-frameshift <jats:italic>CALR<\/jats:italic> mutations were diagnosed with reactive thrombocytosis and MPN unclassifiable, respectively. Our study showed that <jats:italic>CALR<\/jats:italic> mutations are important, non-invasive diagnostic indicators of ET and can aid in its diagnosis. Moreover, the type of <jats:italic>CALR<\/jats:italic> mutation must be accurately defined, as non-frameshift mutations may not be associated with ET. Finally, <jats:italic>CALR<\/jats:italic> mutation detection should be reserved for patients with high suspicion of clonal haematological disease.<\/jats:p>","DOI":"10.1038\/s41598-019-56236-x","type":"journal-article","created":{"date-parts":[[2019,12,27]],"date-time":"2019-12-27T11:03:12Z","timestamp":1577444592000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["CALR mutations in a cohort of JAK2 V617F negative patients with suspected myeloproliferative neoplasms"],"prefix":"10.1038","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0092-5682","authenticated-orcid":false,"given":"Tanja","family":"Belcic Mikic","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tadej","family":"Pajic","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matjaz","family":"Sever","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2019,12,27]]},"reference":[{"key":"56236_CR1","doi-asserted-by":"publisher","first-page":"2391","DOI":"10.1056\/NEJMoa1312542","volume":"369","author":"J Nangalia","year":"2013","unstructured":"Nangalia, J. et al. Somatic CALR mutations in myeloproliferative neoplasms with nonmutated JAK2. N Engl J Med 369, 2391\u20132405, https:\/\/doi.org\/10.1056\/NEJMoa1312542 (2013).","journal-title":"N Engl J Med"},{"key":"56236_CR2","doi-asserted-by":"publisher","first-page":"2379","DOI":"10.1056\/NEJMoa1311347","volume":"369","author":"T Klampfl","year":"2013","unstructured":"Klampfl, T. et al. Somatic mutations of calreticulin in myeloproliferative neoplasms. N Engl J Med 369, 2379\u20132390, https:\/\/doi.org\/10.1056\/NEJMoa1311347 (2013).","journal-title":"N Engl J Med"},{"key":"56236_CR3","doi-asserted-by":"publisher","first-page":"1933","DOI":"10.1038\/leu.2014.165","volume":"28","author":"M Heuser","year":"2014","unstructured":"Heuser, M. et al. Low frequency of calreticulin mutations in MDS patients. 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