Renin angiotensin system genes are biomarkers for personalized treatment of acute myeloid leukemia with Doxorubicin as well as etoposide

buir.contributor.authorAkbar, Muhammad Waqas
buir.contributor.authorKüçükkaraduman, Barış
buir.contributor.authorİşbilen, Murat
buir.contributor.authorGüre, Ali Osmay
dc.citation.epage17en_US
dc.citation.issueNumberNovemberen_US
dc.citation.spage1en_US
dc.citation.volumeNumber15en_US
dc.contributor.authorTürk, S.
dc.contributor.authorTürk, C.
dc.contributor.authorAkbar, Muhammad Waqas
dc.contributor.authorKüçükkaraduman, Barış
dc.contributor.authorİşbilen, Murat
dc.contributor.authorDemirkol-Canlı, S.
dc.contributor.authorMalkan, Ü. Y.
dc.contributor.authorOkay, M.
dc.contributor.authorUçar, G.
dc.contributor.authorSayınalp, N.
dc.contributor.authorHaznedaroğlu, İ. C.
dc.contributor.authorGüre, Ali Osmay
dc.date.accessioned2021-03-01T12:12:00Z
dc.date.available2021-03-01T12:12:00Z
dc.date.issued2020
dc.departmentDepartment of Molecular Biology and Geneticsen_US
dc.description.abstractDespite the availability of various treatment protocols, response to therapy in patients with Acute Myeloid Leukemia (AML) remains largely unpredictable. Transcriptomic profiling studies have thus far revealed the presence of molecular subtypes of AML that are not accounted for by standard clinical parameters or by routinely used biomarkers. Such molecular subtypes of AML are predicted to vary in response to chemotherapy or targeted therapy. The Renin-Angiotensin System (RAS) is an important group of proteins that play a critical role in regulating blood pressure, vascular resistance and fluid/electrolyte balance. RAS pathway genes are also known to be present locally in tissues such as the bone marrow, where they play an important role in leukemic hematopoiesis. In this study, we asked if the RAS genes could be utilized to predict drug responses in patients with AML. We show that the combined in silico analysis of up to five RAS genes can reliably predict sensitivity to Doxorubicin as well as Etoposide in AML. The same genes could also predict sensitivity to Doxorubicin when tested in vitro. Additionally, gene set enrichment analysis revealed enrichment of TNF-alpha and type-I IFN response genes among sensitive, and TGF-beta and fibronectin related genes in resistant cancer cells. However, this does not seem to reflect an epithelial to mesenchymal transition per se. We also identified that RAS genes can stratify patients with AML into subtypes with distinct prognosis. Together, our results demonstrate that genes present in RAS are biomarkers for drug sensitivity and the prognostication of AML.en_US
dc.identifier.doi10.1371/journal.pone.0242497en_US
dc.identifier.issn1932-6203
dc.identifier.urihttp://hdl.handle.net/11693/75676
dc.language.isoEnglishen_US
dc.publisherPublic Library of Scienceen_US
dc.relation.isversionofhttps://dx.doi.org/10.1371/journal.pone.0242497en_US
dc.source.titlePLoS ONEen_US
dc.subjectGene expressionen_US
dc.subjectLinear regression analysisen_US
dc.subjectRenin-angiotensin systemen_US
dc.subjectAcute myeloid leukemiaen_US
dc.subjectCytotoxicityen_US
dc.subjectCancer drug discoveryen_US
dc.subjectPrognosisen_US
dc.subjectBiomarkersen_US
dc.titleRenin angiotensin system genes are biomarkers for personalized treatment of acute myeloid leukemia with Doxorubicin as well as etoposideen_US
dc.typeArticleen_US

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