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 . .

TY  - JOUR
AU  - Vignjevic, Sanja
AU  - Budec, Mirela
AU  - Marković, Dragana
AU  - Dikic, Dragoslava
AU  - Mitrovic, Olivera
AU  - Mojsilovic, Slavko
AU  - Vranješ-Đurić, Sanja
AU  - Koko, Vesna
AU  - Cokic, Bojana Beleslin
AU  - Cokic, Vladan
AU  - Jovcic, Gordana
PY  - 2014
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/5818
AB  - Psychological stress affects different physiological processes including haematopoiesis. However, erythropoietic effects of chronic psychological stress remain largely unknown. The adult spleen contains a distinct microenvironment favourable for rapid expansion of erythroid progenitors in response to stressful stimuli, and emerging evidence suggests that inappropriate activation of stress erythropoiesis may predispose to leukaemic transformation. We used a mouse model to study the influence of chronic psychological stress on erythropoiesis in the spleen and to investigate potential mediators of observed effects. Adult mice were subjected to 2hrs daily restraint stress for 7 or 14 consecutive days. Our results showed that chronic exposure to restraint stress decreased the concentration of haemoglobin in the blood, elevated circulating levels of erythropoietin and corticosterone, and resulted in markedly increased number of erythroid progenitors and precursors in the spleen. Western blot analysis revealed significantly decreased expression of both erythropoietin receptor and glucocorticoid receptor in the spleen of restrained mice. Furthermore, chronic stress enhanced the expression of stem cell factor receptor in the red pulp. Moreover, chronically stressed animals exhibited significantly increased expression of bone morphogenetic protein 4 (BMP4) in the red pulp as well as substantially enhanced mRNA expression levels of its receptors in the spleen. These findings demonstrate for the first time that chronic psychological stress activates BMP4-dependent extramedullary erythropoiesis and leads to the prolonged activation of stress erythropoiesis pathways. Prolonged activation of these pathways along with an excessive production of immature erythroid cells may predispose chronically stressed subjects to a higher risk of leukaemic transformation.
T2  - Journal of Cellular and Molecular Medicine
T1  - Chronic psychological stress activates BMP4-dependent extramedullary erythropoiesis
VL  - 18
IS  - 1
SP  - 91
EP  - 103
DO  - 10.1111/jcmm.12167
ER  - 

@article{
author = "Vignjevic, Sanja and Budec, Mirela and Marković, Dragana and Dikic, Dragoslava and Mitrovic, Olivera and Mojsilovic, Slavko and Vranješ-Đurić, Sanja and Koko, Vesna and Cokic, Bojana Beleslin and Cokic, Vladan and Jovcic, Gordana",
year = "2014",
abstract = "Psychological stress affects different physiological processes including haematopoiesis. However, erythropoietic effects of chronic psychological stress remain largely unknown. The adult spleen contains a distinct microenvironment favourable for rapid expansion of erythroid progenitors in response to stressful stimuli, and emerging evidence suggests that inappropriate activation of stress erythropoiesis may predispose to leukaemic transformation. We used a mouse model to study the influence of chronic psychological stress on erythropoiesis in the spleen and to investigate potential mediators of observed effects. Adult mice were subjected to 2hrs daily restraint stress for 7 or 14 consecutive days. Our results showed that chronic exposure to restraint stress decreased the concentration of haemoglobin in the blood, elevated circulating levels of erythropoietin and corticosterone, and resulted in markedly increased number of erythroid progenitors and precursors in the spleen. Western blot analysis revealed significantly decreased expression of both erythropoietin receptor and glucocorticoid receptor in the spleen of restrained mice. Furthermore, chronic stress enhanced the expression of stem cell factor receptor in the red pulp. Moreover, chronically stressed animals exhibited significantly increased expression of bone morphogenetic protein 4 (BMP4) in the red pulp as well as substantially enhanced mRNA expression levels of its receptors in the spleen. These findings demonstrate for the first time that chronic psychological stress activates BMP4-dependent extramedullary erythropoiesis and leads to the prolonged activation of stress erythropoiesis pathways. Prolonged activation of these pathways along with an excessive production of immature erythroid cells may predispose chronically stressed subjects to a higher risk of leukaemic transformation.",
journal = "Journal of Cellular and Molecular Medicine",
title = "Chronic psychological stress activates BMP4-dependent extramedullary erythropoiesis",
volume = "18",
number = "1",
pages = "91-103",
doi = "10.1111/jcmm.12167"
}

Vignjevic, S., Budec, M., Marković, D., Dikic, D., Mitrovic, O., Mojsilovic, S., Vranješ-Đurić, S., Koko, V., Cokic, B. B., Cokic, V.,& Jovcic, G.. (2014). Chronic psychological stress activates BMP4-dependent extramedullary erythropoiesis. in Journal of Cellular and Molecular Medicine, 18(1), 91-103.
https://doi.org/10.1111/jcmm.12167

Vignjevic S, Budec M, Marković D, Dikic D, Mitrovic O, Mojsilovic S, Vranješ-Đurić S, Koko V, Cokic BB, Cokic V, Jovcic G. Chronic psychological stress activates BMP4-dependent extramedullary erythropoiesis. in Journal of Cellular and Molecular Medicine. 2014;18(1):91-103.
doi:10.1111/jcmm.12167 .

Vignjevic, Sanja, Budec, Mirela, Marković, Dragana, Dikic, Dragoslava, Mitrovic, Olivera, Mojsilovic, Slavko, Vranješ-Đurić, Sanja, Koko, Vesna, Cokic, Bojana Beleslin, Cokic, Vladan, Jovcic, Gordana, "Chronic psychological stress activates BMP4-dependent extramedullary erythropoiesis" in Journal of Cellular and Molecular Medicine, 18, no. 1 (2014):91-103,
https://doi.org/10.1111/jcmm.12167 . .