{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,16]],"date-time":"2026-06-16T04:15:14Z","timestamp":1781583314643,"version":"3.54.5"},"reference-count":66,"publisher":"Public Library of Science (PLoS)","issue":"11","license":[{"start":{"date-parts":[[2020,11,25]],"date-time":"2020-11-25T00:00:00Z","timestamp":1606262400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"The Scientific and Technological Council of Turkey","award":["116S350"],"award-info":[{"award-number":["116S350"]}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:p>Despite 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 <jats:italic>in silico<\/jats:italic> 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 <jats:italic>in vitro<\/jats:italic>. 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.<\/jats:p>","DOI":"10.1371\/journal.pone.0242497","type":"journal-article","created":{"date-parts":[[2020,11,25]],"date-time":"2020-11-25T18:24:34Z","timestamp":1606328674000},"page":"e0242497","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":21,"title":["Renin angiotensin system genes are biomarkers for personalized treatment of acute myeloid leukemia with Doxorubicin as well as etoposide"],"prefix":"10.1371","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3843-4173","authenticated-orcid":true,"given":"Seyhan","family":"Turk","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Can","family":"Turk","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Muhammad Waqas","family":"Akbar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Baris","family":"Kucukkaraduman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Murat","family":"Isbilen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0200-7962","authenticated-orcid":true,"given":"Secil","family":"Demirkol Canli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5444-4895","authenticated-orcid":true,"given":"Umit Yavuz","family":"Malkan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mufide","family":"Okay","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gulberk","family":"Ucar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nilgun","family":"Sayinalp","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ibrahim Celalettin","family":"Haznedaroglu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ali Osmay","family":"Gure","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2020,11,25]]},"reference":[{"key":"pone.0242497.ref001","doi-asserted-by":"crossref","DOI":"10.1002\/9781119645214","volume-title":"Cancer: Prevention, Early Detection, Treatment and Recovery","author":"GS Stein","year":"2019"},{"issue":"6","key":"pone.0242497.ref002","doi-asserted-by":"crossref","first-page":"586","DOI":"10.1038\/ng.2651","article-title":"A panoramic view of acute myeloid leukemia","volume":"45","author":"SJ Chen","year":"2013","journal-title":"Nat Genet"},{"issue":"7","key":"pone.0242497.ref003","doi-asserted-by":"crossref","first-page":"e441","DOI":"10.1038\/bcj.2016.50","article-title":"\u2018Acute myeloid leukemia: a comprehensive review and 2016 update\u2019","volume":"6","author":"I De Kouchkovsky","year":"2016","journal-title":"Blood Cancer J"},{"key":"pone.0242497.ref004","unstructured":"Chu E. 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