Angiogenic factors are increased in circulating granulocytes and CD34+ cells of myeloproliferative neoplasms

Suboticki, Tijana and Mitrovic Ajtic, Olivera and Beleslin-Cokic, Bojana B. and Nienhold, Ronny and Diklic, Milos and Djikic, Dragoslava and Lekovic, Danijela and Bulat, Tanja and Markovic, Dragana and Gotic, Mirjana and Noguchi, Constance T. and Schechter, Alan N. and Skoda, Radek C. and Cokic, Vladan P.. (2017) Angiogenic factors are increased in circulating granulocytes and CD34+ cells of myeloproliferative neoplasms. Molecular carcinogenesis, 56 (2). pp. 567-579.

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Official URL: https://edoc.unibas.ch/62458/

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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-inducible factor-1alpha (HIF-1alpha), 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-1alpha 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-1alpha 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 TGFbeta 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.
Faculties and Departments:03 Faculty of Medicine > Departement Biomedizin > Department of Biomedicine, University Hospital Basel > Experimental Hematology (Skoda)
UniBasel Contributors:Skoda, Radek C.
Item Type:Article, refereed
Article Subtype:Research Article
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:16 Apr 2020 12:43
Deposited On:16 Apr 2020 12:43

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