TY  - JOUR
AU  - Subotički, Tijana
AU  - Mitrović-Ajtić, Olivera
AU  - Beleslin-Čokić, Bojana B.
AU  - Nienhold, Ronny
AU  - Diklić, Miloš
AU  - Đikić, Dragoslava
AU  - Leković, Danijela
AU  - Bulat, Tanja M.
AU  - Marković, Dragana
AU  - Gotić, Mirjana
AU  - Noguchi, Constance T.
AU  - Schechter, Alan N.
AU  - Skoda, Radek C.
AU  - Čokić, Vladan
PY  - 2017
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/1395
AB  - 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-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.
T2  - Molecular Carcinogenesis
T1  - Angiogenic factors are increased in circulating granulocytes and CD34(+) cells of myeloproliferative neoplasms
VL  - 56
IS  - 2
SP  - 567
EP  - 579
DO  - 10.1002/mc.22517
ER  - 

@article{
author = "Subotički, Tijana and Mitrović-Ajtić, Olivera and Beleslin-Čokić, Bojana B. and Nienhold, Ronny and Diklić, Miloš and Đikić, Dragoslava and Leković, Danijela and Bulat, Tanja M. and Marković, Dragana and Gotić, Mirjana and Noguchi, Constance T. and Schechter, Alan N. and Skoda, Radek C. and Čokić, Vladan",
year = "2017",
abstract = "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-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.",
journal = "Molecular Carcinogenesis",
title = "Angiogenic factors are increased in circulating granulocytes and CD34(+) cells of myeloproliferative neoplasms",
volume = "56",
number = "2",
pages = "567-579",
doi = "10.1002/mc.22517"
}

Subotički, T., Mitrović-Ajtić, O., Beleslin-Čokić, B. B., Nienhold, R., Diklić, M., Đikić, D., Leković, D., Bulat, T. M., Marković, D., Gotić, M., Noguchi, C. T., Schechter, A. N., Skoda, R. C.,& Čokić, V.. (2017). Angiogenic factors are increased in circulating granulocytes and CD34(+) cells of myeloproliferative neoplasms. in Molecular Carcinogenesis, 56(2), 567-579.
https://doi.org/10.1002/mc.22517

Subotički T, Mitrović-Ajtić O, Beleslin-Čokić BB, Nienhold R, Diklić M, Đikić D, Leković D, Bulat TM, Marković D, Gotić M, Noguchi CT, Schechter AN, Skoda RC, Čokić V. Angiogenic factors are increased in circulating granulocytes and CD34(+) cells of myeloproliferative neoplasms. in Molecular Carcinogenesis. 2017;56(2):567-579.
doi:10.1002/mc.22517 .

Subotički, Tijana, Mitrović-Ajtić, Olivera, Beleslin-Čokić, Bojana B., Nienhold, Ronny, Diklić, Miloš, Đikić, Dragoslava, Leković, Danijela, Bulat, Tanja M., Marković, Dragana, Gotić, Mirjana, Noguchi, Constance T., Schechter, Alan N., Skoda, Radek C., Čokić, Vladan, "Angiogenic factors are increased in circulating granulocytes and CD34(+) cells of myeloproliferative neoplasms" in Molecular Carcinogenesis, 56, no. 2 (2017):567-579,
https://doi.org/10.1002/mc.22517 . .