Angiogenic factors are increased in circulating granulocytes and CD34(+) cells of myeloproliferative neoplasms
2017
Аутори
Subotički, TijanaMitrović-Ajtić, Olivera
Beleslin-Čokić, Bojana
Nienhold, Ronny
Diklić, Miloš
Đikić, Dragoslava
Leković, Danijela
Bulat, Tanja
Marković, Dragana
Gotić, Mirjana
Noguchi, Constance T.
Schechter, Alan N.
Skoda, Radek C.
Čokić, Vladan
Чланак у часопису (Објављена верзија)
Метаподаци
Приказ свих података о документуАпстракт
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 afte...r 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.
Кључне речи:
angiogenesis / myeloproliferative neoplasm / HIF-1 / VEGF / eNOSИзвор:
Molecular Carcinogenesis, 2017, 56, 2, 567-579Издавач:
- Wiley-Blackwell, Hoboken
Финансирање / пројекти:
- Испитивање патогенезе хематолошких малигнитета (RS-MESTD-Basic Research (BR or ON)-175053)
- Swiss National Science Foundation (SNSF) European Commission [IZ73Z0_152420]
- Intramural Research Program at the National Institute of Diabetes and Digestive and Kidney Diseases, NIH, Bethesda, USA
DOI: 10.1002/mc.22517
ISSN: 0899-1987
PubMed: 27341002
WoS: 000392521800022
Scopus: 2-s2.0-84978198792
Институција/група
Institut za medicinska istraživanjaTY - JOUR AU - Subotički, Tijana AU - Mitrović-Ajtić, Olivera AU - Beleslin-Čokić, Bojana AU - Nienhold, Ronny AU - Diklić, Miloš AU - Đikić, Dragoslava AU - Leković, Danijela AU - Bulat, Tanja AU - Marković, Dragana AU - Gotić, Mirjana AU - Noguchi, Constance T. AU - Schechter, Alan N. AU - Skoda, Radek C. AU - Čokić, Vladan PY - 2017 UR - http://rimi.imi.bg.ac.rs/handle/123456789/807 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. PB - Wiley-Blackwell, Hoboken T2 - Molecular Carcinogenesis T1 - Angiogenic factors are increased in circulating granulocytes and CD34(+) cells of myeloproliferative neoplasms EP - 579 IS - 2 SP - 567 VL - 56 DO - 10.1002/mc.22517 ER -
@article{ author = "Subotički, Tijana and Mitrović-Ajtić, Olivera and Beleslin-Čokić, Bojana and Nienhold, Ronny and Diklić, Miloš and Đikić, Dragoslava and Leković, Danijela and Bulat, Tanja 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.", publisher = "Wiley-Blackwell, Hoboken", journal = "Molecular Carcinogenesis", title = "Angiogenic factors are increased in circulating granulocytes and CD34(+) cells of myeloproliferative neoplasms", pages = "579-567", number = "2", volume = "56", doi = "10.1002/mc.22517" }
Subotički, T., Mitrović-Ajtić, O., Beleslin-Čokić, B., Nienhold, R., Diklić, M., Đikić, D., Leković, D., Bulat, T., 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 Wiley-Blackwell, Hoboken., 56(2), 567-579. https://doi.org/10.1002/mc.22517
Subotički T, Mitrović-Ajtić O, Beleslin-Čokić B, Nienhold R, Diklić M, Đikić D, Leković D, Bulat T, 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, Nienhold, Ronny, Diklić, Miloš, Đikić, Dragoslava, Leković, Danijela, Bulat, Tanja, 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 . .