{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,3]],"date-time":"2026-11-03T20:20:09Z","timestamp":1793737209267,"version":"4.6.1"},"reference-count":120,"publisher":"SAGE Publications","license":[{"start":{"date-parts":[[2019,1,1]],"date-time":"2019-01-01T00:00:00Z","timestamp":1546300800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"funder":[{"DOI":"10.13039\/501100004595","name":"universiti sains malaysia","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004595","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Biomark\ufffdInsights"],"published-print":{"date-parts":[[2019,1]]},"abstract":"<jats:p>Epigenetic alteration has been proposed to give rise to numerous classic hallmarks of cancer. Impaired DNA methylation plays a central role in the onset and progression of several types of malignancies, and DNA methylation is mediated by DNA methyltransferases (DNMTs) consisting of DNMT1, DNMT3A, and DNMT3B. DNMTs are frequently implicated in the pathogenesis and aggressiveness of acute myeloid leukaemia (AML) patients. In this review, we describe and discuss the oncogenic roles of DNMT1, DNMT3A, and DNMT3B in AML. The clinical response predictive roles of DNMTs in clinical trials utilising hypomethylating agents (azacitidine and decitabine) in AML patients are presented. Novel hypomethylating agent (guadecitabine) and experimental DNMT inhibitors in AML are also discussed. In summary, hypermethylation of tumour suppressors mediated by DNMT1 or DNMT3B contributes to the progression and severity of AML (except MLL-AF9 and inv(16)(p13;q22) AML for DNMT3B), while mutation affecting DNMT3A represents an early genetic lesion in the pathogenesis of AML. In clinical trials of AML patients, expression of DNMTs is downregulated by hypomethylating agents while the clinical response predictive roles of DNMT biomarkers remain unresolved. Finally, nucleoside hypomethylating agents have continued to show enhanced responses in clinical trials of AML patients, and novel non-nucleoside DNMT inhibitors have demonstrated cytotoxicity against AML cells in pre-clinical settings.<\/jats:p>","DOI":"10.1177\/1177271919846454","type":"journal-article","created":{"date-parts":[[2019,5,8]],"date-time":"2019-05-08T08:12:25Z","timestamp":1557303145000},"update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":122,"title":["Oncogenic Roles and Inhibitors of DNMT1, DNMT3A, and DNMT3B in Acute Myeloid Leukaemia"],"prefix":"10.1177","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7359-6202","authenticated-orcid":false,"given":"Kah Keng","family":"Wong","sequence":"first","affiliation":[{"name":"Department of Immunology, School of Medical Sciences, Universiti Sains Malaysia, Kubang Kerian, Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charles H","family":"Lawrie","sequence":"additional","affiliation":[{"name":"Nuffield Division of Clinical Laboratory Sciences, Radcliffe Department of Medicine, University of Oxford, John Radcliffe Hospital, Oxford, UK"},{"name":"Oncology Department, Biodonostia Health Research Institute, San Sebastian, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tina M","family":"Green","sequence":"additional","affiliation":[{"name":"Department of Pathology, Odense University Hospital, Odense, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2019,5,8]]},"reference":[{"key":"bibr1-1177271919846454","doi-asserted-by":"publisher","DOI":"10.1016\/j.critrevonc.2017.01.020"},{"key":"bibr2-1177271919846454","doi-asserted-by":"publisher","DOI":"10.1126\/science.aal2380"},{"key":"bibr3-1177271919846454","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2013.04.074"},{"key":"bibr4-1177271919846454","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccell.2017.04.005"},{"key":"bibr5-1177271919846454","doi-asserted-by":"publisher","DOI":"10.1038\/nrg3354"},{"key":"bibr6-1177271919846454","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmb.2017.02.008"},{"key":"bibr7-1177271919846454","doi-asserted-by":"publisher","DOI":"10.1186\/s13072-017-0130-8"},{"key":"bibr8-1177271919846454","doi-asserted-by":"publisher","DOI":"10.2174\/092986710791299966"},{"key":"bibr9-1177271919846454","unstructured":"May O. DNA methylation: fingerprints of the (epi)genome. 2010. Website. https:\/\/www.caymanchem.com\/article\/2153. Accessed March 29, 2019."},{"key":"bibr10-1177271919846454","doi-asserted-by":"publisher","DOI":"10.3389\/fgene.2015.00090"},{"key":"bibr11-1177271919846454","doi-asserted-by":"publisher","DOI":"10.1002\/ajh.24648"},{"key":"bibr12-1177271919846454","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2010.30.1820"},{"key":"bibr13-1177271919846454","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra1406184"},{"key":"bibr14-1177271919846454","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1301689"},{"key":"bibr15-1177271919846454","doi-asserted-by":"publisher","DOI":"10.1038\/sj.leu.2403054"},{"key":"bibr16-1177271919846454","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccr.2009.11.020"},{"key":"bibr17-1177271919846454","doi-asserted-by":"publisher","DOI":"10.1126\/science.1170116"},{"key":"bibr18-1177271919846454","doi-asserted-by":"publisher","DOI":"10.1038\/sj.leu.2402834"},{"key":"bibr19-1177271919846454","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2011-02-339747"},{"key":"bibr20-1177271919846454","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2010.32.7742"},{"key":"bibr21-1177271919846454","doi-asserted-by":"publisher","DOI":"10.1038\/leu.2011.326"},{"key":"bibr22-1177271919846454","doi-asserted-by":"publisher","DOI":"10.1038\/leu.2011.71"},{"key":"bibr23-1177271919846454","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2015-07-604512"},{"key":"bibr24-1177271919846454","doi-asserted-by":"publisher","DOI":"10.1038\/nbt.1678"},{"key":"bibr25-1177271919846454","doi-asserted-by":"publisher","DOI":"10.1186\/s13059-014-0406-2"},{"key":"bibr26-1177271919846454","doi-asserted-by":"publisher","DOI":"10.3390\/ijms18020415"},{"key":"bibr27-1177271919846454","first-page":"53","volume":"6","author":"Malik P","year":"2014","journal-title":"Cancer Manag Res"},{"key":"bibr28-1177271919846454","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmgm.2017.05.014"},{"key":"bibr29-1177271919846454","doi-asserted-by":"publisher","DOI":"10.1016\/j.bmcl.2016.11.023"},{"key":"bibr30-1177271919846454","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0174410"},{"key":"bibr31-1177271919846454","doi-asserted-by":"publisher","DOI":"10.2174\/15680096113139990077"},{"key":"bibr32-1177271919846454","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-16-2304"},{"key":"bibr33-1177271919846454","doi-asserted-by":"crossref","first-page":"e0180142","DOI":"10.1371\/journal.pone.0180142","volume":"12","author":"Li S","year":"2017","journal-title":"PLoS ONE"},{"key":"bibr34-1177271919846454","first-page":"289","volume-title":"Myeloid Leukemia \u2013 Basic Mechanisms of Leukemogenesis","volume":"2011","author":"Fares J"},{"key":"bibr35-1177271919846454","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V97.5.1172"},{"key":"bibr36-1177271919846454","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-17-0235"},{"key":"bibr37-1177271919846454","doi-asserted-by":"publisher","DOI":"10.1007\/s12288-016-0770-z"},{"key":"bibr38-1177271919846454","doi-asserted-by":"publisher","DOI":"10.1038\/leu.2016.349"},{"key":"bibr39-1177271919846454","doi-asserted-by":"publisher","DOI":"10.1038\/leu.2017.307"},{"key":"bibr40-1177271919846454","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.9777"},{"key":"bibr41-1177271919846454","doi-asserted-by":"publisher","DOI":"10.1016\/j.pathol.2017.08.009"},{"key":"bibr42-1177271919846454","doi-asserted-by":"publisher","DOI":"10.1016\/j.prp.2017.10.005"},{"key":"bibr43-1177271919846454","doi-asserted-by":"publisher","DOI":"10.1016\/j.canlet.2014.11.025"},{"key":"bibr44-1177271919846454","doi-asserted-by":"publisher","DOI":"10.3892\/ol.2017.6050"},{"key":"bibr45-1177271919846454","doi-asserted-by":"publisher","DOI":"10.1038\/leu.2017.144"},{"key":"bibr46-1177271919846454","doi-asserted-by":"publisher","DOI":"10.1016\/j.yexmp.2015.03.006"},{"key":"bibr47-1177271919846454","doi-asserted-by":"publisher","DOI":"10.1038\/s41375-018-0119-8"},{"key":"bibr48-1177271919846454","doi-asserted-by":"publisher","DOI":"10.1038\/leu.2017.109"},{"key":"bibr49-1177271919846454","doi-asserted-by":"publisher","DOI":"10.1002\/ajh.25328"},{"key":"bibr50-1177271919846454","doi-asserted-by":"publisher","DOI":"10.1038\/onc.2010.117"},{"key":"bibr51-1177271919846454","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1005143"},{"key":"bibr52-1177271919846454","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2011-07-367961"},{"key":"bibr53-1177271919846454","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1409405"},{"key":"bibr54-1177271919846454","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1408617"},{"key":"bibr55-1177271919846454","doi-asserted-by":"publisher","DOI":"10.1038\/leu.2017.295"},{"key":"bibr56-1177271919846454","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccell.2016.05.003"},{"key":"bibr57-1177271919846454","doi-asserted-by":"publisher","DOI":"10.1158\/2159-8290.CD-16-0008"},{"key":"bibr58-1177271919846454","doi-asserted-by":"publisher","DOI":"10.1038\/leu.2016.160"},{"key":"bibr59-1177271919846454","doi-asserted-by":"publisher","DOI":"10.1038\/bmt.2012.88"},{"key":"bibr60-1177271919846454","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2011.36.9868"},{"key":"bibr61-1177271919846454","doi-asserted-by":"publisher","DOI":"10.1038\/leu.2016.163"},{"key":"bibr62-1177271919846454","first-page":"158","volume":"35","author":"Ardestani MT","year":"2018","journal-title":"Turk J Haematol"},{"key":"bibr63-1177271919846454","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbmt.2015.07.030"},{"key":"bibr64-1177271919846454","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0026906"},{"key":"bibr65-1177271919846454","doi-asserted-by":"publisher","DOI":"10.1038\/leu.2017.200"},{"key":"bibr66-1177271919846454","doi-asserted-by":"publisher","DOI":"10.1002\/pbc.23179"},{"key":"bibr67-1177271919846454","doi-asserted-by":"publisher","DOI":"10.1038\/leu.2017.239"},{"key":"bibr68-1177271919846454","doi-asserted-by":"publisher","DOI":"10.1038\/s41375-018-0084-2"},{"key":"bibr69-1177271919846454","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-018-0081-z"},{"key":"bibr70-1177271919846454","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0051527"},{"key":"bibr71-1177271919846454","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.25475"},{"key":"bibr72-1177271919846454","doi-asserted-by":"publisher","DOI":"10.1038\/leu.2014.267"},{"key":"bibr73-1177271919846454","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccr.2014.02.010"},{"key":"bibr74-1177271919846454","doi-asserted-by":"publisher","DOI":"10.1038\/leu.2014.15"},{"key":"bibr75-1177271919846454","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0074626"},{"key":"bibr76-1177271919846454","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.20176"},{"key":"bibr77-1177271919846454","doi-asserted-by":"publisher","DOI":"10.1038\/leu.2016.112"},{"key":"bibr78-1177271919846454","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2015-07-655928"},{"key":"bibr79-1177271919846454","doi-asserted-by":"publisher","DOI":"10.1172\/JCI57292"},{"key":"bibr80-1177271919846454","doi-asserted-by":"publisher","DOI":"10.1016\/j.bcmd.2007.06.009"},{"key":"bibr81-1177271919846454","doi-asserted-by":"publisher","DOI":"10.1038\/onc.2017.293"},{"key":"bibr82-1177271919846454","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2008-07-170589"},{"key":"bibr83-1177271919846454","doi-asserted-by":"publisher","DOI":"10.1038\/leu.2012.342"},{"key":"bibr84-1177271919846454","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2018.07.133"},{"key":"bibr85-1177271919846454","doi-asserted-by":"publisher","DOI":"10.1186\/s12885-018-4097-z"},{"key":"bibr86-1177271919846454","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2006.09.4169"},{"key":"bibr87-1177271919846454","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2012-03-413898"},{"key":"bibr88-1177271919846454","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1002650107"},{"key":"bibr89-1177271919846454","doi-asserted-by":"publisher","DOI":"10.1111\/bjh.12268"},{"key":"bibr90-1177271919846454","doi-asserted-by":"crossref","first-page":"2594","DOI":"10.1182\/blood.V126.23.2594.2594","volume":"126","author":"Gottipati S","year":"2015","journal-title":"Blood"},{"key":"bibr91-1177271919846454","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2007-03-078576"},{"key":"bibr92-1177271919846454","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2003-03-0687"},{"key":"bibr93-1177271919846454","doi-asserted-by":"publisher","DOI":"10.1038\/leu.2013.173"},{"key":"bibr94-1177271919846454","doi-asserted-by":"publisher","DOI":"10.1172\/JCI69739"},{"key":"bibr95-1177271919846454","doi-asserted-by":"publisher","DOI":"10.1080\/17474086.2018.1453802"},{"key":"bibr96-1177271919846454","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-07-0251"},{"key":"bibr97-1177271919846454","doi-asserted-by":"publisher","DOI":"10.1002\/cncr.31138"},{"key":"bibr98-1177271919846454","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(15)00038-8"},{"key":"bibr99-1177271919846454","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(17)30576-4"},{"key":"bibr100-1177271919846454","doi-asserted-by":"publisher","DOI":"10.3324\/haematol.2018.207118"},{"key":"bibr101-1177271919846454","unstructured":"ClinicalTrials.gov. Phase 3 randomized, open-label study of guadecitabine vs treatment choice in previously treated acute myeloid leukemia. 2016. Website. https:\/\/clinicaltrials.gov\/ct2\/show\/NCT02920008. Accessed March 24, 2019."},{"key":"bibr102-1177271919846454","unstructured":"ClinicalTrials.gov. Phase 1 study of SGI-110 in patients with acute myeloid leukemia. 2014. Website. https:\/\/clinicaltrials.gov\/ct2\/show\/NCT02293993. Accessed March 24, 2019."},{"key":"bibr103-1177271919846454","unstructured":"ClinicalTrials.gov. Guadecitabine extension study. 2018. Website. https:\/\/clinicaltrials.gov\/ct2\/show\/NCT03603964. Accessedarch 24, 2019."},{"key":"bibr104-1177271919846454","unstructured":"ClinicalTrials.gov. SGI-110 and donor lymphocyte infusions (DLI) after allogeneic stem cell transplantation. 2018. Website. https:\/\/clinicaltrials.gov\/ct2\/show\/NCT03454984. Accessed March 24, 2019."},{"key":"bibr105-1177271919846454","unstructured":"ClinicalTrials.gov. Decitabine and talazoparib in untreated AML and R\/R AML (1565GCC). 2019. Website. https:\/\/clinicaltrials.gov\/ct2\/show\/NCT02878785. Accessed March 25, 2019."},{"key":"bibr106-1177271919846454","unstructured":"ClinicalTrials.gov. A trial of epigenetic priming in patients with newly diagnosed acute myeloid leukemia. 2017. Website. https:\/\/clinicaltrials.gov\/ct2\/show\/NCT03164057. Accessed March 24, 2019."},{"key":"bibr107-1177271919846454","unstructured":"ClinicalTrials.gov. Study of SGI-110 in elderly acute myeloid leukemia (AML). 2014. Website. https:\/\/clinicaltrials.gov\/ct2\/show\/NCT02096055. Accessed March 24, 2019."},{"key":"bibr108-1177271919846454","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-13-1391"},{"key":"bibr109-1177271919846454","doi-asserted-by":"publisher","DOI":"10.1038\/nrclinonc.2014.163"},{"key":"bibr110-1177271919846454","doi-asserted-by":"publisher","DOI":"10.1177\/1758835918808509"},{"key":"bibr111-1177271919846454","doi-asserted-by":"publisher","DOI":"10.1016\/j.molonc.2011.07.001"},{"key":"bibr112-1177271919846454","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gku638"},{"key":"bibr113-1177271919846454","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.23386"},{"key":"bibr114-1177271919846454","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.23607"},{"key":"bibr115-1177271919846454","doi-asserted-by":"publisher","DOI":"10.1016\/j.bmc.2009.11.050"},{"key":"bibr116-1177271919846454","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmech.2017.04.017"},{"key":"bibr117-1177271919846454","doi-asserted-by":"publisher","DOI":"10.1021\/jm7015705"},{"key":"bibr118-1177271919846454","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.8210"},{"key":"bibr119-1177271919846454","doi-asserted-by":"publisher","DOI":"10.1111\/cbdd.12741"},{"key":"bibr120-1177271919846454","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2009.10.009"}],"container-title":["Biomarker Insights"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/1177271919846454","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/full-xml\/10.1177\/1177271919846454","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/1177271919846454","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T13:26:16Z","timestamp":1777382776000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.sagepub.com\/doi\/10.1177\/1177271919846454"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,1]]},"references-count":120,"alternative-id":["10.1177\/1177271919846454"],"URL":"https:\/\/doi.org\/10.1177\/1177271919846454","relation":{},"ISSN":["1177-2719","1177-2719"],"issn-type":[{"value":"1177-2719","type":"print"},{"value":"1177-2719","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,1]]},"article-number":"1177271919846454"}}