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Moreover, this compound has been also shown to overcome the resistance of cancer cells to chemotherapeutic agents. ACF has been shown to target hypoxia\u2010inducible factors (HIFs) activity, which are key effectors of hypoxia\u2010mediated chemoresistance. In this study, we showed that ACF inhibits the growth and survival of chronic myeloid leukaemia (CML) and acute myeloid leukaemia (AML) cell lines in normoxic conditions. We further demonstrated that ACF down\u2010regulates STAT5 expression in CML and AML cells but activates STAT3 in CML cells in a HIF\u2010independent manner. In addition, we demonstrated that ACF suppresses the resistance of CML cells to tyrosine kinase inhibitors, such as imatinib. Our data suggest that the dual effect of ACF might be exploited to eradicate de novo or acquired resistance of myeloid leukaemia cells to chemotherapy.<\/jats:p>","DOI":"10.1111\/jcmm.15612","type":"journal-article","created":{"date-parts":[[2020,7,15]],"date-time":"2020-07-15T12:47:21Z","timestamp":1594817241000},"page":"10052-10062","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Acriflavine targets oncogenic STAT5 signaling in myeloid leukemia cells"],"prefix":"10.1111","volume":"24","author":[{"given":"Rawan","family":"Hallal","sequence":"first","affiliation":[{"name":"Universit\u00e9 de Tours EA7501 GICC  Tours France"},{"name":"CNRS ERL7001 LNOx  Tours France"},{"name":"PRASE Lebanese University  Beirut Lebanon"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rawan","family":"Nehme","sequence":"additional","affiliation":[{"name":"Universit\u00e9 de Tours EA7501 GICC  Tours France"},{"name":"CNRS ERL7001 LNOx  Tours France"},{"name":"PRASE Lebanese University  Beirut Lebanon"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marie","family":"Brachet\u2010Botineau","sequence":"additional","affiliation":[{"name":"Universit\u00e9 de Tours EA7501 GICC  Tours France"},{"name":"CNRS ERL7001 LNOx  Tours France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ali","family":"Nehme","sequence":"additional","affiliation":[{"name":"Universit\u00e9 de Tours EA7501 GICC  Tours France"},{"name":"CNRS ERL7001 LNOx  Tours France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hassan","family":"Dakik","sequence":"additional","affiliation":[{"name":"Universit\u00e9 de Tours EA7501 GICC  Tours France"},{"name":"CNRS ERL7001 LNOx  Tours France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Margaux","family":"Deynoux","sequence":"additional","affiliation":[{"name":"Universit\u00e9 de Tours EA7501 GICC  Tours France"},{"name":"CNRS ERL7001 LNOx  Tours France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Persio","family":"Dello Sbarba","sequence":"additional","affiliation":[{"name":"Dipartimento di Scienze Biomediche Sperimentali e Cliniche \u201cMario Serio\u201d Universit\u00e0 degli Studi di Firenze  Florence Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yves","family":"Levern","sequence":"additional","affiliation":[{"name":"INRAE Imagerie en Infectiologie UMR Infectiologie et Sant\u00e9 Publique Universit\u00e9 de Tours  Nouzilly France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazem","family":"Zibara","sequence":"additional","affiliation":[{"name":"PRASE Lebanese University  Beirut Lebanon"},{"name":"Biology Department Faculty of Sciences\u2010I Lebanese University  Beirut Lebanon"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6047-1718","authenticated-orcid":false,"given":"Fabrice","family":"Gouilleux","sequence":"additional","affiliation":[{"name":"Universit\u00e9 de Tours EA7501 GICC  Tours France"},{"name":"CNRS ERL7001 LNOx  Tours France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6984-7096","authenticated-orcid":false,"given":"Fr\u00e9d\u00e9ric","family":"Mazurier","sequence":"additional","affiliation":[{"name":"Universit\u00e9 de Tours EA7501 GICC  Tours France"},{"name":"CNRS ERL7001 LNOx  Tours France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2020,7,15]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/47.1.1"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1349-7006.2011.02097.x"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00109-011-0855-y"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1007\/s13277-014-2156-x"},{"key":"e_1_2_9_6_1","first-page":"3549","article-title":"Antitumor activity of acriflavine in human hepatocellular carcinoma cells","volume":"34","author":"Lee CJ","year":"2014","journal-title":"Anticancer Res"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-017-14990-w"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tranon.2016.11.008"},{"key":"e_1_2_9_9_1","first-page":"10084","article-title":"Acriflavine enhances the antitumor activity of the chemotherapeutic drug 5\u2010fluorouracil in colorectal cancer cells","volume":"15","author":"Zargar P","year":"2018","journal-title":"Oncol Lett"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.canlet.2016.09.029"},{"key":"e_1_2_9_11_1","doi-asserted-by":"crossref","first-page":"220","DOI":"10.1016\/0753-3322(96)87662-1","article-title":"AIDS therapy with two, three or four agent combinations, applied in short sequences, differing from each other by drug rotation. 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