"Direction de la Recherche Clinique" (Grenoble University Hospital)

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"Direction de la Recherche Clinique" (Grenoble University Hospital)

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Quantitative Proteome Heterogeneity in Myeloproliferative Neoplasm Subtypes and Association with JAK2 Mutation Status

Socoro-Yuste, Nuria; Čokić, Vladan; Mondet, Julie; Plo, Isabelle; Mossuz, Pascal

(Amer Assoc Cancer Research, Philadelphia, 2017)

TY  - JOUR
AU  - Socoro-Yuste, Nuria
AU  - Čokić, Vladan
AU  - Mondet, Julie
AU  - Plo, Isabelle
AU  - Mossuz, Pascal
PY  - 2017
UR  - http://rimi.imi.bg.ac.rs/handle/123456789/772
AB  - Apart from well-known genetic abnormalities, several studies have reported variations in protein expression in Philadelphianegative myeloproliferative neoplasm (MPN) patients that could contribute toward their clinical phenotype. In this context, a quantitative mass spectrometry proteomics protocol was used to identify differences in the granulocyte proteome with the goal to characterize the pathogenic role of aberrant protein expression in MPNs. LC/MS-MS (LTQ Orbitrap) coupled to iTRAQ labeling showed significant and quantitative differences in protein content among various MPN subtypes [polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis (PMF)], and according to the genetic status of JAK2 (JAK2V617F presence and JAK2V617F allele burden). A number of differentially expressed proteins were identified, with the most frequent being members of the RAS GTPase family and oxidative stress regulatory proteins. Subsequent analysis found that calreticulin (CALR), known to be involved in calcium homeostasis and apoptotic signaling, was overexpressed in JAK2V617F granulocytes compared with JAK2 wild type and independently of the JAK2V617F allele burden. Finally, it was demonstrated, in a Ba/F3 cell model, that increased calreticulin expression was directly linked to JAK2V617F and could be regulated by JAK2 kinase inhibitors. Implications: In conclusion, these results reveal proteome alterations in MPN granulocytes depending on the phenotype and genotype of patients, highlighting new oncogenic mechanisms associated with JAK2 mutations and overexpression of calreticulin.
PB  - Amer Assoc Cancer Research, Philadelphia
T2  - Molecular Cancer Research
T1  - Quantitative Proteome Heterogeneity in Myeloproliferative Neoplasm Subtypes and Association with JAK2 Mutation Status
EP  - 861
IS  - 7
SP  - 852
VL  - 15
DO  - 10.1158/1541-7786.MCR-16-0495
ER  - 
@article{
author = "Socoro-Yuste, Nuria and Čokić, Vladan and Mondet, Julie and Plo, Isabelle and Mossuz, Pascal",
year = "2017",
abstract = "Apart from well-known genetic abnormalities, several studies have reported variations in protein expression in Philadelphianegative myeloproliferative neoplasm (MPN) patients that could contribute toward their clinical phenotype. In this context, a quantitative mass spectrometry proteomics protocol was used to identify differences in the granulocyte proteome with the goal to characterize the pathogenic role of aberrant protein expression in MPNs. LC/MS-MS (LTQ Orbitrap) coupled to iTRAQ labeling showed significant and quantitative differences in protein content among various MPN subtypes [polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis (PMF)], and according to the genetic status of JAK2 (JAK2V617F presence and JAK2V617F allele burden). A number of differentially expressed proteins were identified, with the most frequent being members of the RAS GTPase family and oxidative stress regulatory proteins. Subsequent analysis found that calreticulin (CALR), known to be involved in calcium homeostasis and apoptotic signaling, was overexpressed in JAK2V617F granulocytes compared with JAK2 wild type and independently of the JAK2V617F allele burden. Finally, it was demonstrated, in a Ba/F3 cell model, that increased calreticulin expression was directly linked to JAK2V617F and could be regulated by JAK2 kinase inhibitors. Implications: In conclusion, these results reveal proteome alterations in MPN granulocytes depending on the phenotype and genotype of patients, highlighting new oncogenic mechanisms associated with JAK2 mutations and overexpression of calreticulin.",
publisher = "Amer Assoc Cancer Research, Philadelphia",
journal = "Molecular Cancer Research",
title = "Quantitative Proteome Heterogeneity in Myeloproliferative Neoplasm Subtypes and Association with JAK2 Mutation Status",
pages = "861-852",
number = "7",
volume = "15",
doi = "10.1158/1541-7786.MCR-16-0495"
}
Socoro-Yuste, N., Čokić, V., Mondet, J., Plo, I.,& Mossuz, P.. (2017). Quantitative Proteome Heterogeneity in Myeloproliferative Neoplasm Subtypes and Association with JAK2 Mutation Status. in Molecular Cancer Research
Amer Assoc Cancer Research, Philadelphia., 15(7), 852-861.
https://doi.org/10.1158/1541-7786.MCR-16-0495
Socoro-Yuste N, Čokić V, Mondet J, Plo I, Mossuz P. Quantitative Proteome Heterogeneity in Myeloproliferative Neoplasm Subtypes and Association with JAK2 Mutation Status. in Molecular Cancer Research. 2017;15(7):852-861.
doi:10.1158/1541-7786.MCR-16-0495 .
Socoro-Yuste, Nuria, Čokić, Vladan, Mondet, Julie, Plo, Isabelle, Mossuz, Pascal, "Quantitative Proteome Heterogeneity in Myeloproliferative Neoplasm Subtypes and Association with JAK2 Mutation Status" in Molecular Cancer Research, 15, no. 7 (2017):852-861,
https://doi.org/10.1158/1541-7786.MCR-16-0495 . .
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