Erythropoietin inhibits chemotherapy-induced cell death and promotes a senescence-like state in leukemia cells

dc.contributor.authorPham, Thuc-Nghi Duc
dc.contributor.authorMa, Weili
dc.contributor.authorMiller, David
dc.contributor.authorKazakova, Lidia
dc.contributor.authorBenchimol, Samuel
dc.date.accessioned2020-03-11T16:52:33Z
dc.date.available2020-03-11T16:52:33Z
dc.date.issued2019-01-08
dc.description.abstractThere are conflicting reports on the adverse effects of erythropoietin (EPO) for the management of cancer-associated anemia. The recognition that erythropoietin receptors (EPORs) are expressed outside the erythroid lineage and concerns that erythropoiesis-stimulating agents (ESAs) may cause tumors to grow and increase the risk of venous thromboembolism have resulted in substantially fewer cancer patients receiving ESA therapy to manage myelosuppressive chemotherapy. In this study, we found that EPO suppresses p53-dependent apoptosis induced by genotoxic (daunorubicin, doxorubicin, and γ-radiation) and non-genotoxic (nutlin-3a) agents and induces a senescence-like state in myeloid leukemia cells. EPO interferes with stress-dependent Mdm2 downregulation and leads to the destabilization of p53 protein. EPO selectively modulates the expression of p53 target genes in response to DNA damage preventing the induction of a number of noncoding RNAs (ncRNAs) previously associated with p53-dependent apoptosis. EPO also enhances the expression of the cyclin-dependent kinase inhibitor p21WAF1 and promotes recruitment of p53 to the p21 promoter. In addition, EPO antagonizes Mcl-1 protein degradation in daunorubicin-treated cells. Hence, EPO signaling targets Mcl-1 expression and the p53-Mdm2 network to promote tumor cell survival.en_US
dc.description.sponsorshipYork University Librariesen_US
dc.identifier.citationCell Death and Disease 10 (2019): 22.en_US
dc.identifier.urihttps://doi.org/10.1038/s41419-018-1274-6en_US
dc.identifier.urihttps://hdl.handle.net/10315/37098
dc.language.isoenen_US
dc.publisherSpringeren_US
dc.rightsAttribution 2.5 Canada*
dc.rights.articlehttps://www.nature.com/articles/s41419-018-1274-6en_US
dc.rights.journalhttps://www.nature.com/cddis/en_US
dc.rights.publisherhttps://www.springernature.com/gpen_US
dc.rights.urihttp://creativecommons.org/licenses/by/2.5/ca/*
dc.titleErythropoietin inhibits chemotherapy-induced cell death and promotes a senescence-like state in leukemia cellsen_US
dc.typeArticleen_US

Files

Original bundle
Now showing 1 - 1 of 1
Loading...
Thumbnail Image
Name:
s41419-018-1274-6.pdf
Size:
2.02 MB
Format:
Adobe Portable Document Format
Description:
License bundle
Now showing 1 - 1 of 1
No Thumbnail Available
Name:
license.txt
Size:
1.83 KB
Format:
Item-specific license agreed upon to submission
Description: