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Microarray and Proteomic Analyses of Myeloproliferative Neoplasms with a Highlight on the mTOR Signaling Pathway

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.

(Public Library Science, San Francisco, 2015)

TY  - 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 . .
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