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This is most well-established in acute myeloid leukemia (AML), where demethylation of\n                  <jats:italic>MYC<\/jats:italic>\n                  is thought to promote leukemogenesis. Using nanopore direct RNA sequencing to quantify m\n                  <jats:sup>6<\/jats:sup>\n                  A transcriptome-wide, we find that m\n                  <jats:sup>6<\/jats:sup>\n                  A stoichiometry, including at\n                  <jats:italic>MYC<\/jats:italic>\n                  -specific sites, remains unaffected by\n                  <jats:italic>FTO<\/jats:italic>\n                  knockdown or pharmacologic inhibition in AML. Conversely, levels of\n                  <jats:italic>N<\/jats:italic>\n                  <jats:sup>6<\/jats:sup>\n                  -2\u2019-O-dimethyladenosine (m\n                  <jats:sup>6<\/jats:sup>\n                  Am) are markedly increased in snRNAs, indicating that m\n                  <jats:sup>6<\/jats:sup>\n                  Am, not m\n                  <jats:sup>6<\/jats:sup>\n                  A, is the major substrate of FTO in AML. We extend these results outside the AML context in\n                  <jats:italic>FTO<\/jats:italic>\n                  knockout brain and HEK293T cells, detecting no selective increases in mRNA m\n                  <jats:sup>6<\/jats:sup>\n                  A but widespread increases in snRNA m\n                  <jats:sup>6<\/jats:sup>\n                  Am levels following FTO depletion. These findings suggest that FTO has minimal ability to erase m\n                  <jats:sup>6<\/jats:sup>\n                  A in mRNA. Instead, the reported biological effects of FTO are likely mediated by demethylation of m\n                  <jats:sup>6<\/jats:sup>\n                  Am.\n                <\/jats:p>","DOI":"10.1101\/2025.10.22.681652","type":"posted-content","created":{"date-parts":[[2025,10,23]],"date-time":"2025-10-23T15:55:15Z","timestamp":1761234915000},"source":"Crossref","is-referenced-by-count":4,"title":["FTO does not function as an m\n                  <sup>6<\/sup>\n                  A eraser in AML: a reassessment using direct RNA nanopore sequencing"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0009-0005-8203-7249","authenticated-orcid":false,"given":"Luke S.","family":"Nicholson","sequence":"first","affiliation":[{"name":"Department of Pharmacology, Weill Cornell Medicine, Cornell University, New York, NY 10065, 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