{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T03:52:10Z","timestamp":1790740330523,"version":"4.1.0"},"reference-count":35,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2020,12,3]],"date-time":"2020-12-03T00:00:00Z","timestamp":1606953600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002661","name":"Fonds De La Recherche Scientifique - FNRS","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100002661","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100005026","name":"Stichting Tegen Kanker","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100005026","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100006282","name":"Koning Boudewijnstichting","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100006282","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J Cellular Molecular Medi"],"published-print":{"date-parts":[[2021,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Cytarabine and daunorubicin are old drugs commonly used in the treatment of acute myeloid leukaemia (AML). Refractory or relapsed disease because of chemotherapy resistance is a major issue. microRNAs (miRNAs) were incriminated in resistance. This study aimed to identify miRNAs involved in chemoresistance in AML patients and to define their target genes. We focused on cytogenetically normal AML patients with wild\u2010type <jats:italic>NPM1<\/jats:italic> without <jats:italic>FLT3<\/jats:italic>\u2010ITD as the treatment of this subset of patients with intermediate\u2010risk cytogenetics is not well established. We analysed baseline AML samples by small RNA sequencing and compared the profile of chemoresistant to chemosensitive AML patients. Among the miRNAs significantly overexpressed in chemoresistant patients, we revealed <jats:italic>miR\u201015a\u20105p<\/jats:italic> and <jats:italic>miR\u201021\u20105p<\/jats:italic> as miRNAs with a major role in chemoresistance in AML. We showed that <jats:italic>miR\u201015a\u20105p<\/jats:italic> and <jats:italic>miR\u201021\u20105p<\/jats:italic> overexpression decreased apoptosis induced by cytarabine and\/or daunorubicin. <jats:italic>PDCD4<\/jats:italic>, <jats:italic>ARL2<\/jats:italic> and <jats:italic>BTG2<\/jats:italic> genes were found to be targeted by <jats:italic>miR\u201015a\u20105p<\/jats:italic>, as well as <jats:italic>PDCD4<\/jats:italic> and <jats:italic>BTG2<\/jats:italic> by <jats:italic>miR\u201021\u20105p<\/jats:italic>. Inhibition experiments of the three target genes reproduced the functional effect of both miRNAs on chemosensitivity. Our study demonstrates that <jats:italic>miR\u201015a\u20105p<\/jats:italic> and <jats:italic>miR\u201021\u20105p<\/jats:italic> are overexpressed in a subgroup of chemoresistant AML patients. Both miRNAs induce chemoresistance by targeting three pro\u2010apoptotic genes <jats:italic>PDCD4<\/jats:italic>, <jats:italic>ARL2<\/jats:italic> and <jats:italic>BTG2<\/jats:italic>.<\/jats:p>","DOI":"10.1111\/jcmm.16110","type":"journal-article","created":{"date-parts":[[2020,12,3]],"date-time":"2020-12-03T17:22:11Z","timestamp":1607016131000},"page":"575-585","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":41,"title":["miR\u201015a\u20105p and miR\u201021\u20105p contribute to chemoresistance in cytogenetically normal acute myeloid leukaemia by targeting PDCD4, ARL2 and BTG2"],"prefix":"10.1111","volume":"25","author":[{"given":"Virginie","family":"Vandewalle","sequence":"first","affiliation":[{"name":"Department of Hematology Cliniques Universitaires Saint\u2010Luc Brussels Belgium"},{"name":"Experimental Medicine Unit de Duve Institute Universit\u00e9 Catholique de Louvain Brussels Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ahmed","family":"Essaghir","sequence":"additional","affiliation":[{"name":"Experimental Medicine Unit de Duve Institute Universit\u00e9 Catholique de Louvain Brussels Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emeline","family":"Bollaert","sequence":"additional","affiliation":[{"name":"Experimental Medicine Unit de Duve Institute Universit\u00e9 Catholique de Louvain Brussels Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandrine","family":"Lenglez","sequence":"additional","affiliation":[{"name":"Experimental Medicine Unit de Duve Institute Universit\u00e9 Catholique de Louvain Brussels Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carlos","family":"Graux","sequence":"additional","affiliation":[{"name":"Department of Hematology CHU UCL Namur (Godinne site) Yvoir Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"H\u00e9l\u00e8ne","family":"Schoemans","sequence":"additional","affiliation":[{"name":"Department of Hematology University Hospitals Leuven and KU Leuven Leuven Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pascale","family":"Saussoy","sequence":"additional","affiliation":[{"name":"Laboratory of Hematology Cliniques Universitaires Saint Luc Brussels Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lucienne","family":"Michaux","sequence":"additional","affiliation":[{"name":"Center for Human Genetics University Hospitals Leuven and KU Leuven Leuven Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter J. M.","family":"Valk","sequence":"additional","affiliation":[{"name":"Department of Hematology Erasmus University Medical Center Rotterdam the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean\u2010Baptiste","family":"Demoulin","sequence":"additional","affiliation":[{"name":"Experimental Medicine Unit de Duve Institute Universit\u00e9 Catholique de Louvain Brussels Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6061-6315","authenticated-orcid":false,"given":"Violaine","family":"Havelange","sequence":"additional","affiliation":[{"name":"Department of Hematology Cliniques Universitaires Saint\u2010Luc Brussels Belgium"},{"name":"Experimental Medicine Unit de Duve Institute Universit\u00e9 Catholique de Louvain Brussels 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