{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T13:00:13Z","timestamp":1789390813799,"version":"build-2803163510"},"reference-count":46,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2016,7,8]],"date-time":"2016-07-08T00:00:00Z","timestamp":1467936000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001711","name":"Schweizerischer Nationalfonds zur F\u00f6rderung der Wissenschaftlichen Forschung","doi-asserted-by":"publisher","award":["IZ73Z0_152420"],"award-info":[{"award-number":["IZ73Z0_152420"]}],"id":[{"id":"10.13039\/501100001711","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000062","name":"National Institute of Diabetes and Digestive and Kidney Diseases","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecular Carcinogenesis"],"published-print":{"date-parts":[[2017,2]]},"abstract":"<jats:sec><jats:label\/><jats:p>It has been shown that angiogenesis and inflammation play an important role in development of most hematological malignancies including the myeloproliferative neoplasm (MPN). The aim of this study was to investigate and correlate the levels of key angiogenic molecules such as hypoxia\u2010inducible factor\u20101\u03b1 (HIF\u20101\u03b1), vascular endothelial growth factor (VEGF) and endothelial nitric oxide synthase (eNOS) in peripheral blood and bone marrow cells of MPN patients, along with <jats:italic>JAK2<\/jats:italic>V617F mutation allele burden and effects of therapy. <jats:italic>HIF\u20101\u03b1<\/jats:italic> and <jats:italic>VEGF<\/jats:italic> gene expression were decreased, while <jats:italic>eNOS<\/jats:italic> mRNA levels were increased in granulocytes of MPN patients. Furthermore, positively correlated and increased VEGF and eNOS protein levels were in negative correlation with HIF\u20101\u03b1 levels in granulocytes of MPN patients. According to immunoblotting, the generally augmented angiogenic factors demonstrated <jats:italic>JAK2<\/jats:italic>V617F allele burden dependence only in granulocytes of PMF. The angiogenic factors were largely reduced after hydroxyurea therapy in granulocytes of MPN patients. Levels of eNOS protein expression were stimulated by Calreticulin mutations in granulocytes of essential thrombocythemia. Immunocytochemical analyses of CD34<jats:sup>+<\/jats:sup> cells showed a more pronounced enhancement of angiogenic factors than in granulocytes. Increased gene expression linked to the proinflammatory TGF\u03b2 and MAPK signaling pathways were detected in CD34<jats:sup>+<\/jats:sup> cells of MPN patients. In conclusion, the angiogenesis is increased in several cell types of MPN patients supported by the transcriptional activation of inflammation\u2010related target genes, and is not limited to bone marrow stroma cells. It also appears that some of the benefit of hydroxyurea therapy of the MPN is mediated by effects on angiogenic factors. \u00a9 2016 Wiley Periodicals, Inc.<\/jats:p><\/jats:sec>","DOI":"10.1002\/mc.22517","type":"journal-article","created":{"date-parts":[[2016,6,24]],"date-time":"2016-06-24T13:07:01Z","timestamp":1466773621000},"page":"567-579","source":"Crossref","is-referenced-by-count":11,"title":["Angiogenic factors are increased in circulating granulocytes and CD34<sup>+<\/sup> cells of myeloproliferative neoplasms"],"prefix":"10.1002","volume":"56","author":[{"given":"Tijana","family":"Suboti\u010dki","sequence":"first","affiliation":[{"name":"Institute for Medical Research University of Belgrade Belgrade Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olivera","family":"Mitrovi\u0107 Ajti\u0107","sequence":"additional","affiliation":[{"name":"Institute for Medical Research University of Belgrade Belgrade Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bojana B.","family":"Beleslin\u2010\u010coki\u0107","sequence":"additional","affiliation":[{"name":"Clinic for Endocrinology, Diabetes and Metabolic Diseases Genetic Laboratory Clinical Center of Serbia Belgrade Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ronny","family":"Nienhold","sequence":"additional","affiliation":[{"name":"Department of Biomedicine Experimental Hematology University Hospital Basel Basel Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Milo\u0161","family":"Dikli\u0107","sequence":"additional","affiliation":[{"name":"Institute for Medical Research University of Belgrade Belgrade Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dragoslava","family":"Djiki\u0107","sequence":"additional","affiliation":[{"name":"Institute for Medical Research University of Belgrade Belgrade Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Danijela","family":"Lekovi\u0107","sequence":"additional","affiliation":[{"name":"Clinic of Hematology Clinical Center of Serbia Belgrade Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tanja","family":"Bulat","sequence":"additional","affiliation":[{"name":"Institute for Nuclear Sciences \u201cVin\u010da\u201d University of Belgrade Belgrade Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dragana","family":"Markovi\u0107","sequence":"additional","affiliation":[{"name":"Institute for Medical Research University of Belgrade Belgrade Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mirjana","family":"Goti\u0107","sequence":"additional","affiliation":[{"name":"Clinic of Hematology Clinical Center of Serbia Belgrade Serbia"},{"name":"Faculty of Medicine University of Belgrade Belgrade Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Constance T.","family":"Noguchi","sequence":"additional","affiliation":[{"name":"Molecular Medicine Branch National Institute of Diabetes and Digestive and Kidney Diseases National Institutes of Health Bethesda Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alan N.","family":"Schechter","sequence":"additional","affiliation":[{"name":"Molecular Medicine Branch National Institute of Diabetes and Digestive and Kidney Diseases National Institutes of Health Bethesda Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Radek C.","family":"Skoda","sequence":"additional","affiliation":[{"name":"Department of Biomedicine Experimental Hematology University Hospital Basel Basel Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vladan P.","family":"\u010coki\u0107","sequence":"additional","affiliation":[{"name":"Institute for Medical Research University of Belgrade Belgrade Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2016,7,8]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.12344"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1093\/jb\/mvs136"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1320243111"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.4161\/15384047.2014.956605"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/leu.2013.24"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1093\/carcin\/bgm232"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0029680"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-12-1554"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-06-1758"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa051113"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(05)71142-9"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2141.2009.07726.x"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.3109\/10428194.2010.500435"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1002\/stem.1661"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.phrs.2008.07.008"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10456-011-9251-z"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1186\/2040-2384-2-10"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1002\/hon.865"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1311347"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0135463"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF03033732"},{"key":"e_1_2_7_23_1","doi-asserted-by":"publisher","DOI":"10.1136\/jcp.2010.083386"},{"key":"e_1_2_7_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.humpath.2006.12.011"},{"key":"e_1_2_7_25_1","doi-asserted-by":"publisher","DOI":"10.1080\/10245330701554664"},{"key":"e_1_2_7_26_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajh.10020"},{"key":"e_1_2_7_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.semcancer.2013.02.005"},{"key":"e_1_2_7_28_1","doi-asserted-by":"publisher","DOI":"10.1001\/archsurg.134.12.1325"},{"key":"e_1_2_7_29_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2012-04-421040"},{"key":"e_1_2_7_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ydbio.2012.10.020"},{"key":"e_1_2_7_31_1","doi-asserted-by":"publisher","DOI":"10.1080\/10428190290016809"},{"key":"e_1_2_7_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccr.2008.01.034"},{"key":"e_1_2_7_33_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V95.1.189"},{"key":"e_1_2_7_34_1","doi-asserted-by":"publisher","DOI":"10.1006\/bbrc.1998.9719"},{"key":"e_1_2_7_35_1","doi-asserted-by":"publisher","DOI":"10.1034\/j.1600-0609.2000.90052.x"},{"key":"e_1_2_7_36_1","doi-asserted-by":"publisher","DOI":"10.1038\/leu.2013.167"},{"key":"e_1_2_7_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9440(10)62237-7"},{"key":"e_1_2_7_38_1","doi-asserted-by":"publisher","DOI":"10.1158\/1535-7163.MCT-12-0862"},{"key":"e_1_2_7_39_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cyto.2010.07.427"},{"key":"e_1_2_7_40_1","doi-asserted-by":"publisher","DOI":"10.1155\/2015\/453020"},{"key":"e_1_2_7_41_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2013-11-539098"},{"key":"e_1_2_7_42_1","doi-asserted-by":"publisher","DOI":"10.1111\/cei.12411"},{"key":"e_1_2_7_43_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2015-09-671172"},{"key":"e_1_2_7_44_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13045-016-0275-0"},{"key":"e_1_2_7_45_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2005-11-4454"},{"key":"e_1_2_7_46_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2012-02-412759"},{"key":"e_1_2_7_47_1","doi-asserted-by":"publisher","DOI":"10.1245\/s10434-008-0243-1"}],"container-title":["Molecular Carcinogenesis"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fmc.22517","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fmc.22517","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/mc.22517","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,3,5]],"date-time":"2024-03-05T13:14:45Z","timestamp":1709644485000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/mc.22517"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2016,7,8]]},"references-count":46,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2017,2]]}},"alternative-id":["10.1002\/mc.22517"],"URL":"https:\/\/doi.org\/10.1002\/mc.22517","archive":["Portico"],"relation":{},"ISSN":["0899-1987","1098-2744"],"issn-type":[{"value":"0899-1987","type":"print"},{"value":"1098-2744","type":"electronic"}],"subject":[],"published":{"date-parts":[[2016,7,8]]}}}