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Microarray and Proteomic Analyses of Myeloproliferative Neoplasms with a Highlight on the mTOR Signaling Pathway
dc.creator | Čokić, Vladan | |
dc.creator | Mossuz, Pascal | |
dc.creator | Han, Jing | |
dc.creator | Socoro, Nuria | |
dc.creator | Beleslin-Čokić, Bojana | |
dc.creator | Mitrović, Olivera | |
dc.creator | Subotički, Tijana | |
dc.creator | Diklić, Miloš | |
dc.creator | Leković, Danijela | |
dc.creator | Gotić, Mirjana | |
dc.creator | Puri, Raj K. | |
dc.creator | Noguchi, Constance T. | |
dc.creator | Schechter, Alan N. | |
dc.date.accessioned | 2021-04-20T12:45:31Z | |
dc.date.available | 2021-04-20T12:45:31Z | |
dc.date.issued | 2015 | |
dc.identifier.issn | 1932-6203 | |
dc.identifier.uri | http://rimi.imi.bg.ac.rs/handle/123456789/670 | |
dc.description.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. | en |
dc.publisher | Public Library Science, San Francisco | |
dc.relation | Intramural Research Program at the National Institute of Diabetes and Digestive and Kidney Diseases, NIH, Bethesda, USA | |
dc.relation | National Institutes of Health | |
dc.relation | info:eu-repo/grantAgreement/MESTD/Basic Research (BR or ON)/175053/RS// | |
dc.rights | openAccess | |
dc.rights.uri | https://creativecommons.org/licenses/by/4.0/ | |
dc.source | PLoS One | |
dc.title | Microarray and Proteomic Analyses of Myeloproliferative Neoplasms with a Highlight on the mTOR Signaling Pathway | en |
dc.type | article | |
dc.rights.license | BY | |
dc.citation.issue | 8 | |
dc.citation.other | 10(8): - | |
dc.citation.rank | M21 | |
dc.citation.volume | 10 | |
dc.identifier.doi | 10.1371/journal.pone.0135463 | |
dc.identifier.fulltext | http://rimi.imi.bg.ac.rs/bitstream/id/510/667.pdf | |
dc.identifier.pmid | 26275051 | |
dc.identifier.scopus | 2-s2.0-84942906963 | |
dc.identifier.wos | 000359493600068 | |
dc.type.version | publishedVersion |