{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T02:28:46Z","timestamp":1791340126044,"version":"4.3.1"},"reference-count":36,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2016,1,22]],"date-time":"2016-01-22T00:00:00Z","timestamp":1453420800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American J Hematol"],"published-print":{"date-parts":[[2016,2]]},"abstract":"<jats:p>Mutations in the calreticulin gene (<jats:italic>CALR<\/jats:italic>) were recently identified in approximately 70\u201380% of patients with <jats:italic>JAK2\u2010<\/jats:italic>V617F\u2010negative essential thrombocytosis and primary myelofibrosis. All frameshift mutations generate a recurring novel C\u2010terminus. Here we provide evidence that mutant calreticulin does not accumulate efficiently in cells and is abnormally enriched in the nucleus and extracellular space compared to wildtype calreticulin. The main determinant of these findings is the loss of the calcium\u2010binding and KDEL domains. Expression of type I mutant <jats:italic>CALR<\/jats:italic> in Ba\/F3 cells confers minimal IL\u20103\u2010independent growth. Interestingly, expression of type I and type II mutant <jats:italic>CALR<\/jats:italic> in a nonhematopoietic cell line does not directly activate JAK\/STAT signaling compared to wildtype <jats:italic>CALR<\/jats:italic> and <jats:italic>JAK2\u2010<\/jats:italic>V617F expression. These results led us to investigate paracrine mechanisms of JAK\/STAT activation. Here we show that conditioned media from cells expressing type I mutant <jats:italic>CALR<\/jats:italic> exaggerate cytokine production from normal monocytes with or without treatment with a toll\u2010like receptor agonist. These effects are not dependent on the novel C\u2010terminus. These studies offer novel insights into the mechanism of JAK\/STAT activation in patients with <jats:italic>JAK2\u2010<\/jats:italic>V617F\u2010negative essential thrombocytosis and primary myelofibrosis. Am. J. Hematol. 91:211\u2013219, 2016. \u00a9 2015 Wiley Periodicals, Inc.<\/jats:p>","DOI":"10.1002\/ajh.24245","type":"journal-article","created":{"date-parts":[[2015,11,17]],"date-time":"2015-11-17T07:18:44Z","timestamp":1447744724000},"page":"211-219","source":"Crossref","is-referenced-by-count":35,"title":["Mutant calreticulin\u2010expressing cells induce monocyte hyperreactivity through a paracrine mechanism"],"prefix":"10.1002","volume":"91","author":[{"given":"Michael R.","family":"Garbati","sequence":"first","affiliation":[{"name":"Knight Cancer Institute, Hematology and Medical Oncology, Oregon Health and Science University Portland Oregon"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Catherine A.","family":"Welgan","sequence":"additional","affiliation":[{"name":"Knight Cancer Institute, Hematology and Medical Oncology, Oregon Health and Science University Portland Oregon"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sally 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