{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,11]],"date-time":"2025-12-11T03:12:29Z","timestamp":1765422749204},"reference-count":35,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2013,4,27]],"date-time":"2013-04-27T00:00:00Z","timestamp":1367020800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Allergy"],"published-print":{"date-parts":[[2013,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Chronic eosinophilic leukemia (<jats:styled-content style=\"fixed-case\">CEL<\/jats:styled-content>) is a myeloproliferative neoplasm characterized by expansion of neoplastic eosinophils, tissue infiltration, and organ damage. In a subset of these patients, the <jats:styled-content style=\"fixed-case\">FIP<\/jats:styled-content>1L1\/<jats:styled-content style=\"fixed-case\">PDGFRA<\/jats:styled-content> (F\/P) oncoprotein is detectable. F\/P exhibits constitutive tyrosine kinase activity and activates a number of signaling pathways. So far, however, little is known about the role of F\/P\u2010dependent proteins in the pathogenesis of <jats:styled-content style=\"fixed-case\">CEL<\/jats:styled-content>.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>A screen for F\/P\u2010dependent cytokines was performed in growth factor\u2010dependent human cell lines lentivirally transduced with F\/P. Signal transduction pathways were characterized in Ba\/F3 cells with doxycycline\u2010inducible expression of F\/P and in <jats:styled-content style=\"fixed-case\">EOL<\/jats:styled-content>\u20101 cells. Cytokine expression was confirmed in patients' material by immunohistochemistry, immunofluorescence, and confocal microscopy. Gene expression analysis, proliferation assays, and chemotaxis assays were used to elucidate paracrine interactions between neoplastic eosinophils and stromal cells.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We show that F\/P upregulates expression of oncostatin M (<jats:styled-content style=\"fixed-case\">OSM<\/jats:styled-content>) in various cell line models in a <jats:styled-content style=\"fixed-case\">STAT<\/jats:styled-content>5\u2010dependent manner. Correspondingly, neoplastic eosinophils in the bone marrow were found to overexpress <jats:styled-content style=\"fixed-case\">OSM<\/jats:styled-content>. <jats:styled-content style=\"fixed-case\">OSM<\/jats:styled-content> derived from F\/P\u00a0+\u00a0cells stimulated proliferation of stromal cells. Moreover, <jats:styled-content style=\"fixed-case\">OSM<\/jats:styled-content>\u2010containing supernatants from F\/P\u00a0+\u00a0cells were found to upregulate production of stromal cell\u2010derived factor\u20101 (SDF\u20101)\/CXCL12 in human fibroblasts. <jats:styled-content style=\"fixed-case\">SDF<\/jats:styled-content>\u20101, in turn, induced migration of <jats:styled-content style=\"fixed-case\">EOL<\/jats:styled-content>\u20101 cells in a dose\u2010dependent manner.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>We have identified a F\/P\u2010driven paracrine interaction between neoplastic eosinophils and stromal cells that may contribute to tissue fibrosis and accumulation of neoplastic eosinophils in <jats:styled-content style=\"fixed-case\">CEL<\/jats:styled-content>.<\/jats:p><\/jats:sec>","DOI":"10.1111\/all.12139","type":"journal-article","created":{"date-parts":[[2013,4,27]],"date-time":"2013-04-27T05:46:46Z","timestamp":1367041606000},"page":"713-723","source":"Crossref","is-referenced-by-count":10,"title":["Oncostatin <scp>M<\/scp> is a <scp>FIP<\/scp>1L1\/<scp>PDGFRA<\/scp>\u2010dependent mediator of cytokine production in chronic eosinophilic leukemia"],"prefix":"10.1111","volume":"68","author":[{"given":"G.","family":"Hoermann","sequence":"first","affiliation":[{"name":"Department of Laboratory Medicine Medical University of Vienna Vienna Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"S.","family":"Cerny\u2010Reiterer","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine I Division of Hematology and Hemostaseology Medical University of Vienna Vienna Austria"},{"name":"Ludwig Boltzmann Cluster Oncology Vienna 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