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Drug resistance and disease recurrence almost invariably occur, highlighting the need for a deeper understanding of these processes. While low O\n                    <jats:sub>2<\/jats:sub>\n                    compartments, such as bone marrow (BM) niches, are well\u2010recognized hosts of drug\u2010resistant leukaemic cells, standard in vitro studies are routinely performed under supra\u2010physiologic (21% O\n                    <jats:sub>2<\/jats:sub>\n                    , ambient air) conditions, which limits clinical translatability. We hereby identify molecular pathways enriched in AML cells that survive acute challenges with classic or targeted therapeutic agents. Experiments took into account variations in O\n                    <jats:sub>2<\/jats:sub>\n                    tension encountered by leukaemic cells in clinical settings. Integrated RNA and protein profiles revealed that lipid biosynthesis, and particularly the cholesterol biogenesis branch, is a particularly therapy\u2010induced vulnerability in AML cells under low O\n                    <jats:sub>2<\/jats:sub>\n                    states. We also demonstrate that the impact of the cytotoxic agent cytarabine is selectively enhanced by a high\u2010potency statin. The cholesterol biosynthesis programme is amenable to additional translational opportunities within the expanding AML therapeutic landscape. Our findings support the further investigation of higher\u2010potency statin (eg rosuvastatin)\u2013based combination therapies to enhance targeting residual AML cells that reside in low O\n                    <jats:sub>2<\/jats:sub>\n                    environments.\n                  <\/jats:p>","DOI":"10.1111\/jcmm.15339","type":"journal-article","created":{"date-parts":[[2020,5,25]],"date-time":"2020-05-25T19:38:57Z","timestamp":1590435537000},"page":"7378-7392","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Classic and targeted anti\u2010leukaemic agents interfere with the cholesterol biogenesis metagene in acute myeloid leukaemia: Therapeutic implications"],"prefix":"10.1111","volume":"24","author":[{"given":"Fangli","family":"Chen","sequence":"first","affiliation":[{"name":"Melvin and Bren Simon Cancer Center Indiana University Indianapolis IN USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0511-9436","authenticated-orcid":false,"given":"Xue","family":"Wu","sequence":"additional","affiliation":[{"name":"Melvin and Bren Simon Cancer Center Indiana University Indianapolis IN USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cristina","family":"Niculite","sequence":"additional","affiliation":[{"name":"Melvin and Bren Simon Cancer Center Indiana University Indianapolis IN USA"},{"name":"University of Medicine and Pharmacy \u2018Carol Davila\u2019 Bucharest Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marilena","family":"Gilca","sequence":"additional","affiliation":[{"name":"Melvin and Bren Simon Cancer Center Indiana University Indianapolis IN USA"},{"name":"University of Medicine and Pharmacy \u2018Carol Davila\u2019 Bucharest Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniela","family":"Petrusca","sequence":"additional","affiliation":[{"name":"Melvin and Bren Simon Cancer Center Indiana University Indianapolis IN USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adriana","family":"Rogozea","sequence":"additional","affiliation":[{"name":"Melvin and Bren Simon Cancer Center Indiana University Indianapolis IN USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susan","family":"Rice","sequence":"additional","affiliation":[{"name":"Melvin and Bren Simon Cancer Center Indiana University Indianapolis IN USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bin","family":"Guo","sequence":"additional","affiliation":[{"name":"Melvin and Bren Simon Cancer Center Indiana University Indianapolis IN USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shawn","family":"Griffin","sequence":"additional","affiliation":[{"name":"Melvin and Bren Simon Cancer Center Indiana University Indianapolis IN USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7427-0578","authenticated-orcid":false,"given":"George A.","family":"Calin","sequence":"additional","affiliation":[{"name":"Division of Cancer Medicine Department of Experimental Therapeutics The University of Texas, MD Anderson Cancer Center Houston TX USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"H. 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