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Because the presence of mdC in the promoter region of a given gene silences its expression, this oxidation goes in hand with the reactivation of such silenced genes. In different highly aggressive cancers such as acute myeloid leukemia (AML) and glioblastoma, loss of TET enzyme function, and therefore reduced hmdC levels pave the way for tumor development. Impairment of TET activity can occur through metabolic inhibition, through loss\u2010of\u2010function mutations in TET genes themselves, and finally through suppression of TET\u2010expression via epigenetic silencing. Reactivation of TET enzyme expression represents a major aim of epigenetic cancer therapy. Here we show that the carbocyclic antimetabolite 5\u2010aza\u20102\u2032deoxycytidine (cAzadC), which is supposed to suppress the methylation of DNA during replication, leads to a substantial increase of TET2 expression and strongly increasing hmdC levels. We show that the treatment with cAzadC goes in hand with the broad reactivation of the cellular antitumor responses. With patient\u2010derived xenograft AML\u2010mouse models, we show that this translates into a strongly improved anticancer effect in vivo.<\/jats:p>","DOI":"10.1002\/anie.6265286","type":"journal-article","created":{"date-parts":[[2026,6,21]],"date-time":"2026-06-21T15:45:29Z","timestamp":1782056729000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Increasing TET Expression and 5\u2010Hydroxymethylcytosine Formation by a Carbocyclic 5\u2010Aza\u20102\u2032\u2010deoxy\u2010cytidine Antimetabolite"],"prefix":"10.1002","volume":"65","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7423-0613","authenticated-orcid":false,"given":"Maike","family":"D\u00e4ther","sequence":"first","affiliation":[{"name":"Institute for Chemical Epigenetics and Center for Nucleic Acid Therapies Department of Chemistry LMU Munich  Munich 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