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Pleiotropic effects of HMAs include global methylome and transcriptome changes. We asked whether in blasts and T-cells from AML patients HMA-induced in vivo demethylation and remethylation occur randomly or non-randomly, and whether gene demethylation is associated with gene induction. Peripheral blood AML blasts from patients receiving decitabine (20\u2009mg\/m<jats:sup>2<\/jats:sup> day 1\u20135) were serially isolated for methylome analyses (days 0, 8 and 15, <jats:italic>n<\/jats:italic>\u2009=\u200928) and methylome-plus-transcriptome analyses (days 0 and 8, <jats:italic>n<\/jats:italic>\u2009=\u200923), respectively. T-cells were isolated for methylome analyses (days 0 and 8; <jats:italic>n<\/jats:italic>\u2009=\u200916). We noted massive, non-random demethylation at day 8, which was variable between patients. In contrast, T-cells disclosed a thousand-fold lesser, random demethylation, indicating selectivity of the demethylation for the malignant blasts. The integrative analysis of DNA demethylation and transcript induction revealed 87 genes displaying a significant inverse correlation, e.g. the tumor suppressor gene <jats:italic>IFI27<\/jats:italic>, whose derepression was validated in two AML cell lines. These results support HMA-induced, non-random early in vivo demethylation events in AML blasts associated with gene induction. Larger patient cohorts are needed to determine whether a demethylation signature may be predictive for response to this treatment.<\/jats:p>","DOI":"10.1038\/s41375-023-01876-2","type":"journal-article","created":{"date-parts":[[2023,4,6]],"date-time":"2023-04-06T19:03:12Z","timestamp":1680807792000},"page":"1018-1027","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["In vivo kinetics of early, non-random methylome and transcriptome changes induced by DNA-hypomethylating treatment in primary AML blasts"],"prefix":"10.1038","volume":"37","author":[{"given":"Gabriele","family":"Greve","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5389-9481","authenticated-orcid":false,"given":"Geoffroy","family":"Andrieux","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8460-0462","authenticated-orcid":false,"given":"Pascal","family":"Schlosser","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nadja","family":"Blagitko-Dorfs","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Usama-Ur","family":"Rehman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tobias","family":"Ma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dietmar","family":"Pfeifer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gerhard","family":"Heil","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andreas","family":"Neubauer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J\u00fcrgen","family":"Krauter","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5318-9044","authenticated-orcid":false,"given":"Michael","family":"Heuser","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Helmut R.","family":"Salih","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2261-9862","authenticated-orcid":false,"given":"Konstanze","family":"D\u00f6hner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2116-5536","authenticated-orcid":false,"given":"Hartmut","family":"D\u00f6hner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7242-7503","authenticated-orcid":false,"given":"Bj\u00f6rn","family":"Hackanson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melanie","family":"Boerries","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1186-1650","authenticated-orcid":false,"given":"Michael","family":"L\u00fcbbert","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2023,4,6]]},"reference":[{"key":"1876_CR1","doi-asserted-by":"publisher","first-page":"103","DOI":"10.1038\/5047","volume":"21","author":"EE Cameron","year":"1999","unstructured":"Cameron EE, Bachman KE, My\u00f6h\u00e4nen S, Herman JG, Baylin SB. 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KD <i>Honoraria:<\/i> Novartis, Janssen, Jazz Pharmaceuticals, Celgene\/BMS, Daiichi Sankyo, Roche. <i>Consultancy:<\/i> CTI BioPharma, Novartis, Janssen, Jazz Pharmaceuticals, Celgene\/BMS, Daiichi Sankyo, Roche, Abbvie <i>Research Funding for Institution:<\/i> Novartis, Celgene\/BMS, Astellas, Agios. HD <i>Honoraria:<\/i> AbbVie, Agios, Amgen, Astellas, AstraZeneca, BMS, Jazz Pharmaceuticals, Novartis, Daiichi Sankyo, Gilead, Janssen, Servier, Syndax. <i>Consultancy:<\/i> AbbVie, Agios, Amgen, Astellas, Berlin-Chemie, BMS, Jazz Pharmaceuticals, Novartis, Daiichi Sankyo, Gilead, Janssen, Servier, Syndax. <i>Research Funding:<\/i> AbbVie, Agios, Amgen, Astellas, Berlin-Chemie, BMS, Jazz Pharmaceuticals, Novartis, Kronos Bio, Pfizer. BH <i>Honoraria<\/i>: Roche, Boehringer Ingelheim, MSD, Bristol-Myers Squibb, Pfizer. <i>Research Funding:<\/i> Boehringer Ingelheim. <i>Travel, Accommodations, Expenses<\/i>: Novartis, Bristol-Myers Squibb. ML <i>Research Funding:<\/i> Janssen. <i>Consultancy:<\/i> Janssen. <i>Study Drug:<\/i> Cheplapharm, TEVA. All other authors declare no potential conflicts of interest.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}]}}