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dc.creatorSubotički, Tijana
dc.creatorMitrović-Ajtić, Olivera
dc.creatorBeleslin-Čokić, Bojana B.
dc.creatorNienhold, Ronny
dc.creatorDiklić, Miloš
dc.creatorĐikić, Dragoslava
dc.creatorLeković, Danijela
dc.creatorBulat, Tanja M.
dc.creatorMarković, Dragana
dc.creatorGotić, Mirjana
dc.creatorNoguchi, Constance T.
dc.creatorSchechter, Alan N.
dc.creatorSkoda, Radek C.
dc.creatorČokić, Vladan
dc.date.accessioned2018-03-01T17:21:53Z
dc.date.available2018-03-01T17:21:53Z
dc.date.issued2017
dc.identifier.issn0899-1987
dc.identifier.issn1098-2744
dc.identifier.urihttps://vinar.vin.bg.ac.rs/handle/123456789/1395
dc.description.abstractIt 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-inducible factor-1 (HIF-1), vascular endothelial growth factor (VEGF) and endothelial nitric oxide synthase (eNOS) in peripheral blood and bone marrow cells of MPN patients, along with JAK2V617F mutation allele burden and effects of therapy. HIF-1 and VEGF gene expression were decreased, while eNOS 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-1 levels in granulocytes of MPN patients. According to immunoblotting, the generally augmented angiogenic factors demonstrated JAK2V617F 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(+) cells showed a more pronounced enhancement of angiogenic factors than in granulocytes. Increased gene expression linked to the proinflammatory TGF and MAPK signaling pathways were detected in CD34(+) cells of MPN patients. In conclusion, the angiogenesis is increased in several cell types of MPN patients supported by the transcriptional activation of inflammation-related 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. (c) 2016 Wiley Periodicals, Inc.en
dc.relationinfo:eu-repo/grantAgreement/MESTD/Basic Research (BR or ON)/175053/RS//
dc.relationSwiss National Science Foundation [IZ73Z0_152420], National Institute of Diabetes and Digestive and Kidney Diseases
dc.rightsrestrictedAccessen
dc.sourceMolecular Carcinogenesisen
dc.subjectangiogenesisen
dc.subjectmyeloproliferative neoplasmen
dc.subjectHIF-1en
dc.subjectVEGFen
dc.subjecteNOSen
dc.titleAngiogenic factors are increased in circulating granulocytes and CD34(+) cells of myeloproliferative neoplasmsen
dc.typearticleen
dc.rights.licenseARR
dcterms.abstractAјтиц, Оливера Митровиц; Лековиц, Данијела; Белеслин-Цокиц, Бојана Б.; Булат Тања М.; Суботицки, Тијана; Цокиц, Владан П.; Ниенхолд, Роннy; Сцхецхтер, Aлан Н.; Ногуцхи, Цонстанце Т.; Дјикиц, Драгослава; Скода, Радек Ц.; Готиц, Мирјана; Марковиц, Драгана; Диклиц, Милос;
dc.citation.volume56
dc.citation.issue2
dc.citation.spage567
dc.citation.epage579
dc.identifier.wos000392521800022
dc.identifier.doi10.1002/mc.22517
dc.citation.rankM21
dc.identifier.pmid27341002
dc.type.versionpublishedVersion
dc.identifier.scopus2-s2.0-84978198792


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