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Despite its functional importance in various fundamental bioprocesses, the studies of m<sup>6</sup>A in cancer have been limited. Here we show that FTO, as an m<sup>6</sup>A demethylase, plays a critical oncogenic role in acute myeloid leukemia (AML). FTO is highly expressed in AMLs with t(11q23)/MLL rearrangements, t(15;17)/PML-RARA, FLT3-ITD, and/or NPM1 mutations. FTO enhances leukemic oncogene-mediated cell transformation and leukemogenesis, and inhibits all-trans-retinoic acid (ATRA)-induced AML cell differentiation, through regulating expression of targets such as ASB2 and RARA by reducing m<sup>6</sup>A levels in these mRNA transcripts. Collectively, our study demonstrates the functional importance of the m<sup>6</sup>A methylation and the corresponding proteins in cancer, and provides profound insights into leukemogenesis and drug response.","is_dataset_classified":null,"base_score":7.40184157874383,"endowment":7.40184157874383,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"28017614","pmcid":"PMC5234852","openalex_id":"https://openalex.org/W2563912688","authors":[],"funders":[{"funder_name":"NIH","grant_id":"CA178454","title":null},{"funder_name":"NIH","grant_id":"CA182528","title":null},{"funder_name":"NIH","grant_id":"CA214965","title":null},{"funder_name":"NIH","grant_id":"GM071440","title":null},{"funder_name":"Foundation of Innovation Team for Basic and Clinical Research of Zhejiang Province","grant_id":"2011R50015","title":null},{"funder_name":"NCI NIH HHS","grant_id":"R01 CA214965","title":null},{"funder_name":"NCI NIH HHS","grant_id":"R01 CA122623","title":null},{"funder_name":"NCI NIH HHS","grant_id":"R01 CA182528","title":null},{"funder_name":"NCI NIH HHS","grant_id":"T32 CA009594","title":null},{"funder_name":"NCI NIH HHS","grant_id":"R01 CA178454","title":null},{"funder_name":"NCI NIH HHS","grant_id":"R01 CA211614","title":null},{"funder_name":"NCI NIH HHS","grant_id":"R01 CA116097","title":null},{"funder_name":"NIGMS NIH HHS","grant_id":"R01 GM071440","title":null},{"funder_name":"National Institutes of Health","grant_id":"1R01CA214965-01","title":"The role and mechanism of FTO in leukemogenesis and drug response"},{"funder_name":"National Institutes of Health","grant_id":"5R01CA182528-05","title":"Potential therapeutic implications of targeting miR-150 in acute myeloid leukemia"},{"funder_name":"National Institutes of Health","grant_id":"7R01CA178454-06","title":"The role and functional mechanism of TET1 in MLL-rearranged leukemia"},{"funder_name":"Howard Hughes Medical Institute","grant_id":"","title":null},{"funder_name":"Gabrielle&apos;s Angel Foundation for Cancer Research","grant_id":"","title":null},{"funder_name":"China Scholarship Council","grant_id":"","title":null},{"funder_name":"Leukemia &amp; Lymphoma Society","grant_id":"","title":null},{"funder_name":"ACS-IL Research Scholar","grant_id":"","title":null},{"funder_name":"LLS Translational Research","grant_id":"","title":null},{"funder_name":"American Cancer Society","grant_id":"","title":null},{"funder_name":"Howard Hughes Medical Institute","grant_id":"","title":null}],"total_grants":24,"fwci":41.235,"citation_percentile":0.99891186,"influential_citations":0,"citation_trend":[{"year":2017,"count":36},{"year":2018,"count":88},{"year":2019,"count":133},{"year":2020,"count":240},{"year":2021,"count":329},{"year":2022,"count":276},{"year":2023,"count":204},{"year":2024,"count":189},{"year":2025,"count":101},{"year":2026,"count":40}],"oa_status":"closed","license":"Elsevier Non-Commercial","oa_locations":[{"url":"https://api.elsevier.com/content/article/PII:S1535610816305608?httpAccept=text/xml","host_type":"publisher"},{"url":"https://api.elsevier.com/content/article/PII:S1535610816305608?httpAccept=text/plain","host_type":"publisher"},{"url":"https://doi.org/10.1016/j.ccell.2016.11.017","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/28017614","host_type":"repository"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/5234852","host_type":"repository"},{"url":"http://www.cell.com/article/S1535610816305608/pdf","host_type":""},{"url":"https://dx.doi.org/10.1016/j.ccell.2016.11.017","host_type":""}],"fields_of_study":["RNA modifications and cancer","Cancer-related gene regulation","Epigenetics and DNA Methylation","0301 basic medicine","0303 health sciences","03 medical and health sciences","Adenosine","Alpha-Ketoglutarate-Dependent Dioxygenase FTO","Apoptosis","Cell Proliferation","Humans","Leukemia, Myeloid, Acute","Methylation","Nucleophosmin","Retinoic Acid Receptor alpha","Suppressor of Cytokine Signaling Proteins","Transcriptome","Tretinoin"],"mesh_terms":["Alpha-Ketoglutarate-Dependent Dioxygenase FTO","Retinoic Acid Receptor alpha","Nucleophosmin","Adenosine","Humans","Methylation","Tretinoin","Leukemia, Myeloid, Acute","Apoptosis","Cell Proliferation","Suppressor of Cytokine Signaling Proteins","Transcriptome"],"keywords":["Demethylase","Myeloid leukemia","N6-Methyladenosine","Biology","Cancer research","RNA methylation","Myeloid","Oncogene","Leukemia","Retinoic acid","RNA","Cell","Methylation","Cell biology","Epigenetics","Cell cycle","Gene","Genetics","Methyltransferase","Cell differentiation","AMl","ATRA","Leukemogenesis","Rna Stability","Rara","Fto","Rna Modification","M6a","Asb2","Adenosine","Retinoic Acid Receptor alpha","Alpha-Ketoglutarate-Dependent Dioxygenase FTO","Apoptosis","Suppressor of Cytokine Signaling Proteins","Tretinoin","Leukemia, Myeloid, Acute","Humans","Transcriptome","Nucleophosmin","Cell Proliferation"],"sdg_mappings":[{"sdg_number":3,"sdg_label":"3. 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