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Emerging data suggest that mitochondrial oxidative phosphorylation (mtOXPHOS) plays a significant role in AML tumorigenesis, progression, and resistance to chemotherapies. However, how the mtOXPHOS is regulated in AML cells is not well understood. In this study, we investigated the oncogenic functions of ERR\u03b1 in AML by combining in silico, in vitro, and in vivo analyses and showed ERR\u03b1 is a key regulator of mtOXPHOS in AML cells. The increased ERR\u03b1 level was associated with worse clinical outcomes of AML patients. Single cell RNA-Seq analysis of human primary AML cells indicated that ERR\u03b1-expressing cancer cells had significantly higher mtOXPHOS enrichment scores. Blockade of ERR\u03b1 by pharmacologic inhibitor (XCT-790) or gene silencing suppressed mtOXPHOS and increased anti-leukemic effects in vitro and in xenograft mouse models.<\/jats:p>","DOI":"10.1186\/s13045-022-01372-7","type":"journal-article","created":{"date-parts":[[2022,10,26]],"date-time":"2022-10-26T06:03:45Z","timestamp":1666764225000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["Targeting ERR\u03b1 promotes cytotoxic effects against acute myeloid leukemia through suppressing mitochondrial oxidative phosphorylation"],"prefix":"10.1186","volume":"15","author":[{"given":"Wonhyoung","family":"Seo","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seungyeul","family":"Yoo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi","family":"Zhong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sang-Hee","family":"Lee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Soo-Yeon","family":"Woo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hee-Seon","family":"Choi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Minho","family":"Won","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Taylor","family":"Roh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sang Min","family":"Jeon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kyeong Tae","family":"Kim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Prashanta","family":"Silwal","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Min Joung","family":"Lee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun Young","family":"Heo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nathan","family":"Lawlor","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sup","family":"Kim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dongjun","family":"Lee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jin-Man","family":"Kim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ik-Chan","family":"Song","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eun-Kyeong","family":"Jo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2022,10,26]]},"reference":[{"key":"1372_CR1","doi-asserted-by":"publisher","first-page":"70","DOI":"10.1016\/j.blre.2019.04.005","volume":"36","author":"RM Shallis","year":"2019","unstructured":"Shallis RM, et al. Epidemiology of acute myeloid leukemia: recent progress and enduring challenges. Blood Rev. 2019;36:70\u201387.","journal-title":"Blood Rev"},{"issue":"10","key":"1372_CR2","doi-asserted-by":"publisher","first-page":"e427","DOI":"10.1016\/S2352-3026(15)00148-9","volume":"2","author":"J Versluis","year":"2015","unstructured":"Versluis J, et al. Post-remission treatment with allogeneic stem cell transplantation in patients aged 60 years and older with acute myeloid leukaemia: a time-dependent analysis. Lancet Haematol. 2015;2(10):e427\u201336.","journal-title":"Lancet Haematol"},{"issue":"5","key":"1372_CR3","doi-asserted-by":"publisher","first-page":"674","DOI":"10.1016\/j.ccr.2011.10.015","volume":"20","author":"M Skrtic","year":"2011","unstructured":"Skrtic M, et al. Inhibition of mitochondrial translation as a therapeutic strategy for human acute myeloid leukemia. 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Endocr Relat Cancer. 2006;13(Suppl 1):S25-32.","journal-title":"Endocr Relat Cancer"}],"container-title":["Journal of Hematology &amp; Oncology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s13045-022-01372-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s13045-022-01372-7\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s13045-022-01372-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,10,26]],"date-time":"2022-10-26T06:04:55Z","timestamp":1666764295000},"score":1,"resource":{"primary":{"URL":"https:\/\/jhoonline.biomedcentral.com\/articles\/10.1186\/s13045-022-01372-7"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,10,26]]},"references-count":12,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2022,12]]}},"alternative-id":["1372"],"URL":"https:\/\/doi.org\/10.1186\/s13045-022-01372-7","relation":{},"ISSN":["1756-8722"],"issn-type":[{"value":"1756-8722","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,10,26]]},"assertion":[{"value":"11 July 2022","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"13 October 2022","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"26 October 2022","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The research is approved by IRB (CNUH2018-08-013-012) of Chungnam National University Hospital. The AML\/ALL patients samples were obtained with patients informed consent. All experiments were conducted as per the declaration of Helsinki. For the mouse experiments, all animals (6\u2009~\u20098\u00a0weeks old) were housed under a specific pathogen-free environment, and all the in vivo experiments were reviewed and approved by Institutional Animal Care and Use Committee, CNU School of Medicine, Daejeon, Korea (CNUH-020-A0054).","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"All authors approved and directly participated in the planning, execution and\/or analysis of the data presented in this study. The content of this manuscript has not been previously published and is not under consideration for publication elsewhere.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"S.Y., Y.Z., N.L., and J.Z. are employees of Sema4, a for-profit organization that promotes personalized patient care through information-driven insights. Other authors declare that they have no competing interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"156"}}