Bone marrow microvessel density and plasma angiogenic factors in myeloproliferative neoplasms: clinicopathological and molecular correlations
Само за регистроване кориснике
2017
Аутори
Leković, DanijelaGotić, Mirjana
Skoda, Radek C.
Beleslin-Čokić, Bojana
Milić, Nataša
Mitrović-Ajtić, Olivera
Nienhold, Ronny
Sefer, Dijana
Subotički, Tijana
Kovačić, Marijana
Marković, Dragana
Diklić, Miloš
Čokić, Vladan
Чланак у часопису (Објављена верзија)
Метаподаци
Приказ свих података о документуАпстракт
Increased angiogenesis in BCR-ABL1 negative myeloproliferative neoplasms (MPNs) has been recognized, but its connection with clinical and molecular markers needs to be defined. The aims of study were to (1) assess bone marrow (BM) angiogenesis measured by microvessel density (MVD) using CD34 and CD105 antibodies; (2) analyze correlation of MVD with plasma angiogenic factors including vascular endothelial growth factor, basic fibroblast growth factor, and interleukin-8; (3) examine the association of MVD with clinicopathological and molecular markers. We examined 90 de novo MPN patients (30 polycythemia vera (PV), primary myelofibrosis (PMF), essential thrombocythemia (ET)) and 10 age-matched controls. MVD was analyzed by immunohistochemistry "hot spot" method, angiogenic factors by immunoassay and JAK2V617F, and CALR mutations by DNA sequencing and allelic PCR. MVD was significantly increased in MPNs compared to controls (PMF gt PV gt ET). Correlation between MVD and plasma angioge...nic factors was found in MPNs. MVD was significantly increased in patients with JAK2V617F mutation and correlated with JAK2 mutant allele burden (CD34-MVD: rho = 0.491, p lt 0.001; CD105-MVD: rho = 0.276, p = 0.02) but not with CALR mutation. MVD correlated with leukocyte count, serum lactate dehydrogenase, hepatomegaly, and splenomegaly. BM fibrosis was significantly associated with CD34-MVD, CD105-MVD, interleukin-8, and JAK2 mutant allele burden. JAK2 homozygote status had positive predictive value (100%) for BM fibrosis. Patients with prefibrotic PMF had significantly higher MVD than patients with ET, and we could recommend MVD to be additional histopathological marker to distinguish these two entities. This study also highlights the strong correlation of MVD with plasma angiogenic factors, JAK2 mutant allele burden, and BM fibrosis in MPNs.
Кључне речи:
Myeloproliferative neoplasms / Angiogenesis / Microvessel density / JAK2V617F / CALRИзвор:
Annals of Hematology, 2017, 96, 3, 393-404Издавач:
- Springer, New York
Финансирање / пројекти:
- Испитивање патогенезе хематолошких малигнитета (RS-MESTD-Basic Research (BR or ON)-175053)
- Swiss National Science Foundation through Joint research project (SCOPES) [IZ73Z0_152420/1]
DOI: 10.1007/s00277-016-2890-9
ISSN: 0939-5555
PubMed: 27924369
WoS: 000394104500008
Scopus: 2-s2.0-85001816366
Институција/група
Institut za medicinska istraživanjaTY - JOUR AU - Leković, Danijela AU - Gotić, Mirjana AU - Skoda, Radek C. AU - Beleslin-Čokić, Bojana AU - Milić, Nataša AU - Mitrović-Ajtić, Olivera AU - Nienhold, Ronny AU - Sefer, Dijana AU - Subotički, Tijana AU - Kovačić, Marijana AU - Marković, Dragana AU - Diklić, Miloš AU - Čokić, Vladan PY - 2017 UR - http://rimi.imi.bg.ac.rs/handle/123456789/804 AB - Increased angiogenesis in BCR-ABL1 negative myeloproliferative neoplasms (MPNs) has been recognized, but its connection with clinical and molecular markers needs to be defined. The aims of study were to (1) assess bone marrow (BM) angiogenesis measured by microvessel density (MVD) using CD34 and CD105 antibodies; (2) analyze correlation of MVD with plasma angiogenic factors including vascular endothelial growth factor, basic fibroblast growth factor, and interleukin-8; (3) examine the association of MVD with clinicopathological and molecular markers. We examined 90 de novo MPN patients (30 polycythemia vera (PV), primary myelofibrosis (PMF), essential thrombocythemia (ET)) and 10 age-matched controls. MVD was analyzed by immunohistochemistry "hot spot" method, angiogenic factors by immunoassay and JAK2V617F, and CALR mutations by DNA sequencing and allelic PCR. MVD was significantly increased in MPNs compared to controls (PMF gt PV gt ET). Correlation between MVD and plasma angiogenic factors was found in MPNs. MVD was significantly increased in patients with JAK2V617F mutation and correlated with JAK2 mutant allele burden (CD34-MVD: rho = 0.491, p lt 0.001; CD105-MVD: rho = 0.276, p = 0.02) but not with CALR mutation. MVD correlated with leukocyte count, serum lactate dehydrogenase, hepatomegaly, and splenomegaly. BM fibrosis was significantly associated with CD34-MVD, CD105-MVD, interleukin-8, and JAK2 mutant allele burden. JAK2 homozygote status had positive predictive value (100%) for BM fibrosis. Patients with prefibrotic PMF had significantly higher MVD than patients with ET, and we could recommend MVD to be additional histopathological marker to distinguish these two entities. This study also highlights the strong correlation of MVD with plasma angiogenic factors, JAK2 mutant allele burden, and BM fibrosis in MPNs. PB - Springer, New York T2 - Annals of Hematology T1 - Bone marrow microvessel density and plasma angiogenic factors in myeloproliferative neoplasms: clinicopathological and molecular correlations EP - 404 IS - 3 SP - 393 VL - 96 DO - 10.1007/s00277-016-2890-9 ER -
@article{ author = "Leković, Danijela and Gotić, Mirjana and Skoda, Radek C. and Beleslin-Čokić, Bojana and Milić, Nataša and Mitrović-Ajtić, Olivera and Nienhold, Ronny and Sefer, Dijana and Subotički, Tijana and Kovačić, Marijana and Marković, Dragana and Diklić, Miloš and Čokić, Vladan", year = "2017", abstract = "Increased angiogenesis in BCR-ABL1 negative myeloproliferative neoplasms (MPNs) has been recognized, but its connection with clinical and molecular markers needs to be defined. The aims of study were to (1) assess bone marrow (BM) angiogenesis measured by microvessel density (MVD) using CD34 and CD105 antibodies; (2) analyze correlation of MVD with plasma angiogenic factors including vascular endothelial growth factor, basic fibroblast growth factor, and interleukin-8; (3) examine the association of MVD with clinicopathological and molecular markers. We examined 90 de novo MPN patients (30 polycythemia vera (PV), primary myelofibrosis (PMF), essential thrombocythemia (ET)) and 10 age-matched controls. MVD was analyzed by immunohistochemistry "hot spot" method, angiogenic factors by immunoassay and JAK2V617F, and CALR mutations by DNA sequencing and allelic PCR. MVD was significantly increased in MPNs compared to controls (PMF gt PV gt ET). Correlation between MVD and plasma angiogenic factors was found in MPNs. MVD was significantly increased in patients with JAK2V617F mutation and correlated with JAK2 mutant allele burden (CD34-MVD: rho = 0.491, p lt 0.001; CD105-MVD: rho = 0.276, p = 0.02) but not with CALR mutation. MVD correlated with leukocyte count, serum lactate dehydrogenase, hepatomegaly, and splenomegaly. BM fibrosis was significantly associated with CD34-MVD, CD105-MVD, interleukin-8, and JAK2 mutant allele burden. JAK2 homozygote status had positive predictive value (100%) for BM fibrosis. Patients with prefibrotic PMF had significantly higher MVD than patients with ET, and we could recommend MVD to be additional histopathological marker to distinguish these two entities. This study also highlights the strong correlation of MVD with plasma angiogenic factors, JAK2 mutant allele burden, and BM fibrosis in MPNs.", publisher = "Springer, New York", journal = "Annals of Hematology", title = "Bone marrow microvessel density and plasma angiogenic factors in myeloproliferative neoplasms: clinicopathological and molecular correlations", pages = "404-393", number = "3", volume = "96", doi = "10.1007/s00277-016-2890-9" }
Leković, D., Gotić, M., Skoda, R. C., Beleslin-Čokić, B., Milić, N., Mitrović-Ajtić, O., Nienhold, R., Sefer, D., Subotički, T., Kovačić, M., Marković, D., Diklić, M.,& Čokić, V.. (2017). Bone marrow microvessel density and plasma angiogenic factors in myeloproliferative neoplasms: clinicopathological and molecular correlations. in Annals of Hematology Springer, New York., 96(3), 393-404. https://doi.org/10.1007/s00277-016-2890-9
Leković D, Gotić M, Skoda RC, Beleslin-Čokić B, Milić N, Mitrović-Ajtić O, Nienhold R, Sefer D, Subotički T, Kovačić M, Marković D, Diklić M, Čokić V. Bone marrow microvessel density and plasma angiogenic factors in myeloproliferative neoplasms: clinicopathological and molecular correlations. in Annals of Hematology. 2017;96(3):393-404. doi:10.1007/s00277-016-2890-9 .
Leković, Danijela, Gotić, Mirjana, Skoda, Radek C., Beleslin-Čokić, Bojana, Milić, Nataša, Mitrović-Ajtić, Olivera, Nienhold, Ronny, Sefer, Dijana, Subotički, Tijana, Kovačić, Marijana, Marković, Dragana, Diklić, Miloš, Čokić, Vladan, "Bone marrow microvessel density and plasma angiogenic factors in myeloproliferative neoplasms: clinicopathological and molecular correlations" in Annals of Hematology, 96, no. 3 (2017):393-404, https://doi.org/10.1007/s00277-016-2890-9 . .