{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T15:32:47Z","timestamp":1791819167802,"version":"4.3.4"},"reference-count":22,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2021,5,3]],"date-time":"2021-05-03T00:00:00Z","timestamp":1620000000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["American J Hematol"],"published-print":{"date-parts":[[2021,6]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Myeloproliferative neoplasms (MPNs) are characterized by a pathologic expansion of myeloid lineages. Mutations in\n                    <jats:italic>JAK2<\/jats:italic>\n                    ,\n                    <jats:italic>CALR<\/jats:italic>\n                    and\n                    <jats:italic>MPL<\/jats:italic>\n                    genes are known to be three prominent MPN disease drivers. Mutant CALR (mutCALR) is an oncoprotein that interacts with and activates the thrombopoietin receptor (MPL) and represents an attractive target for targeted therapy of CALR mutated MPN. We generated a transgenic murine model with conditional expression of the human mutant exon 9 (del52) from the murine endogenous\n                    <jats:italic>Calr<\/jats:italic>\n                    locus. These mice develop essential thrombocythemia like phenotype with marked thrombocytosis and megakaryocytosis. The disease exacerbates with age showing prominent signs of splenomegaly and anemia. The disease is transplantable and mutCALR stem cells show proliferative advantage when compared to wild type stem cells. Transcriptome profiling of hematopoietic stem cells revealed oncogenic and inflammatory gene expression signatures. To demonstrate the applicability of the transgenic animals for immunotherapy, we treated mice with monoclonal antibody raised against the human mutCALR. The antibody treatment lowered platelet and stem cell counts in mutant mice. Secretion of mutCALR did not constitute a significant antibody sink. This animal model not only recapitulates human MPN but also serves as a relevant model for testing immunotherapeutic strategies targeting epitopes of the human mutCALR.\n                  <\/jats:p>","DOI":"10.1002\/ajh.26171","type":"journal-article","created":{"date-parts":[[2021,3,24]],"date-time":"2021-03-24T15:14:16Z","timestamp":1616598856000},"page":"698-707","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["Hematopoietic expression of a chimeric murine\u2010human\n                    <scp>CALR<\/scp>\n                    oncoprotein allows the assessment of\n                    <scp>anti\u2010CALR<\/scp>\n                    antibody immunotherapies in vivo"],"prefix":"10.1002","volume":"96","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0907-3308","authenticated-orcid":false,"given":"Sarada","family":"Achyutuni","sequence":"first","affiliation":[{"name":"Department of Laboratory Medicine Medical University of Vienna  Vienna Austria"},{"name":"CeMM Research Centre for Molecular Medicine of the Austrian Academy of Sciences  Vienna Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5545-5673","authenticated-orcid":false,"given":"Harini","family":"Nivarthi","sequence":"additional","affiliation":[{"name":"CeMM Research Centre for Molecular Medicine of the Austrian Academy of Sciences  Vienna Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Majoros","sequence":"additional","affiliation":[{"name":"MyeloPro Diagnostics and Research GmbH  Vienna Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eva","family":"Hug","sequence":"additional","affiliation":[{"name":"MyeloPro Diagnostics and Research GmbH  Vienna 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J","family":"Binder","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine Medical University of Vienna  Vienna Austria"},{"name":"CeMM Research Centre for Molecular Medicine of the Austrian Academy of Sciences  Vienna Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christoph","family":"Bock","sequence":"additional","affiliation":[{"name":"CeMM Research Centre for Molecular Medicine of the Austrian Academy of Sciences  Vienna Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oleh","family":"Zagrijtschuk","sequence":"additional","affiliation":[{"name":"MyeloPro Diagnostics and Research GmbH  Vienna Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6997-8539","authenticated-orcid":false,"given":"Robert","family":"Kralovics","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine Medical University of Vienna  Vienna 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