Microarray and Proteomic Analyses of Myeloproliferative Neoplasms with a Highlight on the mTOR Signaling Pathway
2015
Аутори
Čokić, VladanMossuz, Pascal
Han, Jing
Socoro, Nuria
Beleslin-Čokić, Bojana
Mitrović, Olivera
Subotički, Tijana
Diklić, Miloš
Leković, Danijela
Gotić, Mirjana
Puri, Raj K.
Noguchi, Constance T.
Schechter, Alan N.
Чланак у часопису (Објављена верзија)
Метаподаци
Приказ свих података о документуАпстракт
The gene and protein expression profiles in myeloproliferative neoplasms (MPNs) may reveal gene and protein markers of a potential clinical relevance in diagnosis, treatment and prediction of response to therapy. Using cDNA microarray analysis of 25,100 unique genes, we studied the gene expression profile of CD34(+) cells and granulocytes obtained from peripheral blood of subjects with essential thrombocythemia (ET), polycythemia vera (PV) and primary myelofibrosis (PMF). The microarray analyses of the CD34(+) cells and granulocytes were performed from 20 de novo MPN subjects: JAK2 positive ET, PV, PMF subjects, and JAK2 negative ET/PMF subjects. The granulocytes for proteomic studies were pooled in 4 groups: PV with JAK2 mutant allele burden above 80%, ET with JAK2 mutation, PMF with JAK2 mutation and ET/PMF with no JAK2 mutation. The number of differentially regulated genes was about two fold larger in CD34(+) cells compared to granulocytes. Thirty-six genes (including RUNX1, TNFRSF1...9) were persistently highly expressed, while 42 genes (including FOXD4, PDE4A) were underexpressed both in CD34(+) cells and granulocytes. Using proteomic studies, significant up-regulation was observed for MAPK and PI3K/AKT signaling regulators that control myeloid cell apoptosis and proliferation: RAC2, MNDA, S100A8/9, CORO1A, and GNAI2. When the status of the mTOR signaling pathway related genes was analyzed, PI3K/AKT regulators were preferentially up-regulated in CD34(+) cells of MPNs, with down-regulated major components of the protein complex EIF4F. Molecular profiling of CD34(+) cells and granulocytes of MPN determined gene expression patterns beyond their recognized function in disease pathogenesis that included dominant up-regulation of PI3K/AKT signaling.
Извор:
PLoS One, 2015, 10, 8Издавач:
- Public Library Science, San Francisco
Финансирање / пројекти:
- Intramural Research Program at the National Institute of Diabetes and Digestive and Kidney Diseases, NIH, Bethesda, USA
- National Institutes of Health
- Испитивање патогенезе хематолошких малигнитета (RS-MESTD-Basic Research (BR or ON)-175053)
DOI: 10.1371/journal.pone.0135463
ISSN: 1932-6203
PubMed: 26275051
WoS: 000359493600068
Scopus: 2-s2.0-84942906963
Институција/група
Institut za medicinska istraživanjaTY - JOUR AU - Čokić, Vladan AU - Mossuz, Pascal AU - Han, Jing AU - Socoro, Nuria AU - Beleslin-Čokić, Bojana AU - Mitrović, Olivera AU - Subotički, Tijana AU - Diklić, Miloš AU - Leković, Danijela AU - Gotić, Mirjana AU - Puri, Raj K. AU - Noguchi, Constance T. AU - Schechter, Alan N. PY - 2015 UR - http://rimi.imi.bg.ac.rs/handle/123456789/670 AB - The gene and protein expression profiles in myeloproliferative neoplasms (MPNs) may reveal gene and protein markers of a potential clinical relevance in diagnosis, treatment and prediction of response to therapy. Using cDNA microarray analysis of 25,100 unique genes, we studied the gene expression profile of CD34(+) cells and granulocytes obtained from peripheral blood of subjects with essential thrombocythemia (ET), polycythemia vera (PV) and primary myelofibrosis (PMF). The microarray analyses of the CD34(+) cells and granulocytes were performed from 20 de novo MPN subjects: JAK2 positive ET, PV, PMF subjects, and JAK2 negative ET/PMF subjects. The granulocytes for proteomic studies were pooled in 4 groups: PV with JAK2 mutant allele burden above 80%, ET with JAK2 mutation, PMF with JAK2 mutation and ET/PMF with no JAK2 mutation. The number of differentially regulated genes was about two fold larger in CD34(+) cells compared to granulocytes. Thirty-six genes (including RUNX1, TNFRSF19) were persistently highly expressed, while 42 genes (including FOXD4, PDE4A) were underexpressed both in CD34(+) cells and granulocytes. Using proteomic studies, significant up-regulation was observed for MAPK and PI3K/AKT signaling regulators that control myeloid cell apoptosis and proliferation: RAC2, MNDA, S100A8/9, CORO1A, and GNAI2. When the status of the mTOR signaling pathway related genes was analyzed, PI3K/AKT regulators were preferentially up-regulated in CD34(+) cells of MPNs, with down-regulated major components of the protein complex EIF4F. Molecular profiling of CD34(+) cells and granulocytes of MPN determined gene expression patterns beyond their recognized function in disease pathogenesis that included dominant up-regulation of PI3K/AKT signaling. PB - Public Library Science, San Francisco T2 - PLoS One T1 - Microarray and Proteomic Analyses of Myeloproliferative Neoplasms with a Highlight on the mTOR Signaling Pathway IS - 8 VL - 10 DO - 10.1371/journal.pone.0135463 ER -
@article{ author = "Čokić, Vladan and Mossuz, Pascal and Han, Jing and Socoro, Nuria and Beleslin-Čokić, Bojana and Mitrović, Olivera and Subotički, Tijana and Diklić, Miloš and Leković, Danijela and Gotić, Mirjana and Puri, Raj K. and Noguchi, Constance T. and Schechter, Alan N.", year = "2015", abstract = "The gene and protein expression profiles in myeloproliferative neoplasms (MPNs) may reveal gene and protein markers of a potential clinical relevance in diagnosis, treatment and prediction of response to therapy. Using cDNA microarray analysis of 25,100 unique genes, we studied the gene expression profile of CD34(+) cells and granulocytes obtained from peripheral blood of subjects with essential thrombocythemia (ET), polycythemia vera (PV) and primary myelofibrosis (PMF). The microarray analyses of the CD34(+) cells and granulocytes were performed from 20 de novo MPN subjects: JAK2 positive ET, PV, PMF subjects, and JAK2 negative ET/PMF subjects. The granulocytes for proteomic studies were pooled in 4 groups: PV with JAK2 mutant allele burden above 80%, ET with JAK2 mutation, PMF with JAK2 mutation and ET/PMF with no JAK2 mutation. The number of differentially regulated genes was about two fold larger in CD34(+) cells compared to granulocytes. Thirty-six genes (including RUNX1, TNFRSF19) were persistently highly expressed, while 42 genes (including FOXD4, PDE4A) were underexpressed both in CD34(+) cells and granulocytes. Using proteomic studies, significant up-regulation was observed for MAPK and PI3K/AKT signaling regulators that control myeloid cell apoptosis and proliferation: RAC2, MNDA, S100A8/9, CORO1A, and GNAI2. When the status of the mTOR signaling pathway related genes was analyzed, PI3K/AKT regulators were preferentially up-regulated in CD34(+) cells of MPNs, with down-regulated major components of the protein complex EIF4F. Molecular profiling of CD34(+) cells and granulocytes of MPN determined gene expression patterns beyond their recognized function in disease pathogenesis that included dominant up-regulation of PI3K/AKT signaling.", publisher = "Public Library Science, San Francisco", journal = "PLoS One", title = "Microarray and Proteomic Analyses of Myeloproliferative Neoplasms with a Highlight on the mTOR Signaling Pathway", number = "8", volume = "10", doi = "10.1371/journal.pone.0135463" }
Čokić, V., Mossuz, P., Han, J., Socoro, N., Beleslin-Čokić, B., Mitrović, O., Subotički, T., Diklić, M., Leković, D., Gotić, M., Puri, R. K., Noguchi, C. T.,& Schechter, A. N.. (2015). Microarray and Proteomic Analyses of Myeloproliferative Neoplasms with a Highlight on the mTOR Signaling Pathway. in PLoS One Public Library Science, San Francisco., 10(8). https://doi.org/10.1371/journal.pone.0135463
Čokić V, Mossuz P, Han J, Socoro N, Beleslin-Čokić B, Mitrović O, Subotički T, Diklić M, Leković D, Gotić M, Puri RK, Noguchi CT, Schechter AN. Microarray and Proteomic Analyses of Myeloproliferative Neoplasms with a Highlight on the mTOR Signaling Pathway. in PLoS One. 2015;10(8). doi:10.1371/journal.pone.0135463 .
Čokić, Vladan, Mossuz, Pascal, Han, Jing, Socoro, Nuria, Beleslin-Čokić, Bojana, Mitrović, Olivera, Subotički, Tijana, Diklić, Miloš, Leković, Danijela, Gotić, Mirjana, Puri, Raj K., Noguchi, Constance T., Schechter, Alan N., "Microarray and Proteomic Analyses of Myeloproliferative Neoplasms with a Highlight on the mTOR Signaling Pathway" in PLoS One, 10, no. 8 (2015), https://doi.org/10.1371/journal.pone.0135463 . .