TY  - JOUR
AU  - Yalcin, Safak
AU  - Marinković, Dragan
AU  - Mungamuri, Sathish Kumar
AU  - Zhang, Xin
AU  - Tong, Wei
AU  - Sellers, Rani
AU  - Ghaffari, Saghi
PY  - 2010
UR  - http://rfasper.fasper.bg.ac.rs/handle/123456789/377
AB  - Reactive oxygen species (ROS) participate in normal intracellular signalling and in many diseases including cancer and aging, although the associated mechanisms are not fully understood. Forkhead Box O (FoxO) 3 transcription factor regulates levels of ROS concentrations, and is essential for maintenance of hematopoietic stem cells. Here, we show that loss of Foxo3 causes a myeloproliferative syndrome with splenomegaly and increased hematopoietic progenitors (HPs) that are hypersensitive to cytokines. These mutant HPs contain increased ROS, overactive intracellular signalling through the AKT/mammalian target of rapamycin signalling pathway and relative deficiency of Lnk, a negative regulator of cytokine receptor signalling. In vivo treatment with ROS scavenger N-acetyl-cysteine corrects these biochemical abnormalities and relieves the myeloproliferation. Moreover, enforced expression of Lnk by retroviral transfer corrects the abnormal expansion of Foxo3(-/-) HPs in vivo. Our combined results show that loss of Foxo3 causes increased ROS accumulation in HPs. In turn, this inhibits Lnk expression that contributes to exaggerated cytokine responses that lead to myeloproliferation. Our findings could explain the mechanisms by which mutations that alter Foxo3 function induce malignancy. More generally, the work illustrates how deregulated ROS may contribute to malignant progression. The EMBO Journal (2010) 29, 4118-4131. doi: 10.1038/emboj.2010.292; Published online 26 November 2010
PB  - Wiley, Hoboken
T2  - Embo Journal
T1  - ROS-mediated amplification of AKT/mTOR signalling pathway leads to myeloproliferative syndrome in Foxo3(-/-) mice
EP  - 4131
IS  - 24
SP  - 4118
VL  - 29
DO  - 10.1038/emboj.2010.292
ER  - 

@article{
author = "Yalcin, Safak and Marinković, Dragan and Mungamuri, Sathish Kumar and Zhang, Xin and Tong, Wei and Sellers, Rani and Ghaffari, Saghi",
year = "2010",
abstract = "Reactive oxygen species (ROS) participate in normal intracellular signalling and in many diseases including cancer and aging, although the associated mechanisms are not fully understood. Forkhead Box O (FoxO) 3 transcription factor regulates levels of ROS concentrations, and is essential for maintenance of hematopoietic stem cells. Here, we show that loss of Foxo3 causes a myeloproliferative syndrome with splenomegaly and increased hematopoietic progenitors (HPs) that are hypersensitive to cytokines. These mutant HPs contain increased ROS, overactive intracellular signalling through the AKT/mammalian target of rapamycin signalling pathway and relative deficiency of Lnk, a negative regulator of cytokine receptor signalling. In vivo treatment with ROS scavenger N-acetyl-cysteine corrects these biochemical abnormalities and relieves the myeloproliferation. Moreover, enforced expression of Lnk by retroviral transfer corrects the abnormal expansion of Foxo3(-/-) HPs in vivo. Our combined results show that loss of Foxo3 causes increased ROS accumulation in HPs. In turn, this inhibits Lnk expression that contributes to exaggerated cytokine responses that lead to myeloproliferation. Our findings could explain the mechanisms by which mutations that alter Foxo3 function induce malignancy. More generally, the work illustrates how deregulated ROS may contribute to malignant progression. The EMBO Journal (2010) 29, 4118-4131. doi: 10.1038/emboj.2010.292; Published online 26 November 2010",
publisher = "Wiley, Hoboken",
journal = "Embo Journal",
title = "ROS-mediated amplification of AKT/mTOR signalling pathway leads to myeloproliferative syndrome in Foxo3(-/-) mice",
pages = "4131-4118",
number = "24",
volume = "29",
doi = "10.1038/emboj.2010.292"
}

Yalcin, S., Marinković, D., Mungamuri, S. K., Zhang, X., Tong, W., Sellers, R.,& Ghaffari, S.. (2010). ROS-mediated amplification of AKT/mTOR signalling pathway leads to myeloproliferative syndrome in Foxo3(-/-) mice. in Embo Journal
Wiley, Hoboken., 29(24), 4118-4131.
https://doi.org/10.1038/emboj.2010.292

Yalcin S, Marinković D, Mungamuri SK, Zhang X, Tong W, Sellers R, Ghaffari S. ROS-mediated amplification of AKT/mTOR signalling pathway leads to myeloproliferative syndrome in Foxo3(-/-) mice. in Embo Journal. 2010;29(24):4118-4131.
doi:10.1038/emboj.2010.292 .

Yalcin, Safak, Marinković, Dragan, Mungamuri, Sathish Kumar, Zhang, Xin, Tong, Wei, Sellers, Rani, Ghaffari, Saghi, "ROS-mediated amplification of AKT/mTOR signalling pathway leads to myeloproliferative syndrome in Foxo3(-/-) mice" in Embo Journal, 29, no. 24 (2010):4118-4131,
https://doi.org/10.1038/emboj.2010.292 . .