{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T04:07:39Z","timestamp":1792814859755,"version":"4.5.0"},"reference-count":65,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2026,1,30]],"date-time":"2026-01-30T00:00:00Z","timestamp":1769731200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,1,30]],"date-time":"2026-01-30T00:00:00Z","timestamp":1769731200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Blood Res."],"published-print":{"date-parts":[[2026,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    This review examines the role of METTL3, a core RNA methyltransferase, in therapeutic resistance in acute myeloid leukemia (AML) and discusses emerging strategies to address this challenge. METTL3 regulates N\n                    <jats:sup>6<\/jats:sup>\n                    -methyladenosine (m\n                    <jats:sup>6<\/jats:sup>\n                    A) modifications on transcripts involved in key cellular processes, including apoptosis (BCL2, MCL1), metabolism (PGC-1\u03b1, CSRP1), proliferation (MYC), autophagy (FOXO3), and bone marrow microenvironmental interactions (ITGA4, AKT1). These modifications enhance the stability and translation of resistance-associated genes, supporting leukemic cell survival under treatment pressure. Pharmacological targeting of METTL3 has shown efficacy in preclinical AML models. Inhibitors such as STM2457, METTL3-directed PROTACs, and rational drug combinations with agents including venetoclax, anthracyclines, and ATRA, have reversed resistance phenotypes and impaired leukemic cell fitness. Beyond canonical resistance mechanisms, METTL3 also regulates noncoding RNAs, autophagy, and metabolic\u2013epigenetic crosstalk, including histone lactylation, linking epitranscriptomic regulation to broader resistance pathways. By integrating molecular, cellular, and microenvironmental evidence, this review underscores METTL3 as a central driver of drug resistance and a promising therapeutic target in relapsed or refractory AML. Unlike previous summaries, it highlights the convergence of METTL3-mediated m\n                    <jats:sup>6<\/jats:sup>\n                    A modifications with noncoding RNA regulation, autophagy, and niche adaptation, and critically evaluates emerging therapeutic approaches, including catalytic inhibitors, PROTACs, and natural compounds.\n                  <\/jats:p>","DOI":"10.1007\/s44313-026-00123-8","type":"journal-article","created":{"date-parts":[[2026,1,30]],"date-time":"2026-01-30T08:36:51Z","timestamp":1769762211000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["The role of m6A RNA methyltransferase METTL3 in drug resistance mechanisms in acute myeloid leukemia"],"prefix":"10.1007","volume":"61","author":[{"given":"Suresh","family":"Prajapati","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charmi","family":"Jyotishi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mansi","family":"Patel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1743-4388","authenticated-orcid":false,"given":"Reeshu","family":"Gupta","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,1,30]]},"reference":[{"key":"123_CR1","doi-asserted-by":"publisher","first-page":"896426","DOI":"10.3389\/fonc.2022.896426","volume":"12","author":"J Niu","year":"2022","unstructured":"Niu J, Peng D, Liu L. Drug resistance mechanisms of acute myeloid leukemia stem cells. Front Oncol. 2022;12:896426.","journal-title":"Front Oncol"},{"issue":"1","key":"123_CR2","doi-asserted-by":"publisher","first-page":"9189","DOI":"10.1038\/s41467-024-53629-z","volume":"15","author":"AE Culver-Cochran","year":"2024","unstructured":"Culver-Cochran AE, et al. Chemotherapy resistance in acute myeloid leukemia is mediated by A20 suppression of spontaneous necroptosis. Nat Commun. 2024;15(1):9189.","journal-title":"Nat Commun"},{"key":"123_CR3","doi-asserted-by":"publisher","first-page":"1445794","DOI":"10.3389\/fonc.2024.1445794","volume":"14","author":"P Kaur","year":"2024","unstructured":"Kaur P, et al. Current insights on m6A RNA modification in acute leukemia: therapeutic targets and future prospects. Front Oncol. 2024;14:1445794.","journal-title":"Front Oncol"},{"issue":"7860","key":"123_CR4","doi-asserted-by":"publisher","first-page":"597","DOI":"10.1038\/s41586-021-03536-w","volume":"593","author":"E Yankova","year":"2021","unstructured":"Yankova E, et al. Small-molecule inhibition of METTL3 as a strategy against myeloid leukaemia. Nature. 2021;593(7860):597\u2013601.","journal-title":"Nature"},{"issue":"2","key":"123_CR5","doi-asserted-by":"publisher","first-page":"306","DOI":"10.1016\/j.molcel.2016.05.041","volume":"63","author":"P Wang","year":"2016","unstructured":"Wang P, Doxtader KA, Nam Y. Structural basis for cooperative function of Mettl3 and Mettl14 methyltransferases. Mol Cell. 2016;63(2):306\u201317.","journal-title":"Mol Cell"},{"key":"123_CR6","doi-asserted-by":"publisher","first-page":"10","DOI":"10.1038\/s41421-018-0019-0","volume":"4","author":"Y Yue","year":"2018","unstructured":"Yue Y, et al. Virma mediates preferential m(6)a mrna methylation in 3\u2019UTR and near stop codon and associates with alternative polyadenylation. Cell Discov. 2018;4:10.","journal-title":"Cell Discov"},{"key":"123_CR7","doi-asserted-by":"publisher","first-page":"933332","DOI":"10.3389\/fphar.2022.933332","volume":"13","author":"N Song","year":"2022","unstructured":"Song N, et al. The role of m6A RNA methylation in cancer: implication for nature products anti-cancer research. Front Pharmacol. 2022;13:933332.","journal-title":"Front Pharmacol"},{"issue":"2","key":"123_CR8","doi-asserted-by":"publisher","first-page":"183","DOI":"10.1016\/j.molcel.2016.07.005","volume":"63","author":"KI Zhou","year":"2016","unstructured":"Zhou KI, Pan T. Structures of the m(6)A methyltransferase complex: two subunits with distinct but coordinated roles. Mol Cell. 2016;63(2):183\u20135.","journal-title":"Mol Cell"},{"issue":"1","key":"123_CR9","doi-asserted-by":"publisher","first-page":"334","DOI":"10.1186\/s12964-023-01360-5","volume":"21","author":"Q Jin","year":"2023","unstructured":"Jin Q, Qu H, Quan C. New insights into the regulation of METTL3 and its role in tumors. Cell Commun Signal. 2023;21(1):334.","journal-title":"Cell Commun Signal"},{"key":"123_CR10","doi-asserted-by":"publisher","first-page":"873903","DOI":"10.3389\/fonc.2022.873903","volume":"12","author":"X Wu","year":"2022","unstructured":"Wu X, Ye W, Gong Y. The role of RNA methyltransferase METTL3 in normal and malignant hematopoiesis. Front Oncol. 2022;12:873903.","journal-title":"Front Oncol"},{"issue":"1","key":"123_CR11","doi-asserted-by":"publisher","first-page":"126","DOI":"10.1186\/s12964-025-02130-1","volume":"23","author":"Y Zhong","year":"2025","unstructured":"Zhong Y, et al. Specific sDMA modifications on the RGG\/RG motif of METTL14 regulate its function in AML. Cell Commun Signal. 2025;23(1):126.","journal-title":"Cell Commun Signal"},{"issue":"3","key":"123_CR12","doi-asserted-by":"publisher","first-page":"335","DOI":"10.1016\/j.molcel.2016.03.021","volume":"62","author":"S Lin","year":"2016","unstructured":"Lin S, et al. The m(6)A methyltransferase METTL3 promotes translation in human cancer cells. Mol Cell. 2016;62(3):335\u201345.","journal-title":"Mol Cell"},{"issue":"9","key":"123_CR13","doi-asserted-by":"publisher","first-page":"1014","DOI":"10.1038\/ng.3610","volume":"48","author":"X Zhang","year":"2016","unstructured":"Zhang X, et al. DNMT3A and TET2 compete and cooperate to repress lineage-specific transcription factors in hematopoietic stem cells. Nat Genet. 2016;48(9):1014\u201323.","journal-title":"Nat Genet"},{"issue":"6","key":"123_CR14","doi-asserted-by":"publisher","first-page":"690","DOI":"10.3390\/biomedicines9060690","volume":"9","author":"S Kumar","year":"2021","unstructured":"Kumar S, et al. Immunotherapeutic potential of m6A-Modifiers and MicroRNAs in controlling acute myeloid leukaemia. Biomedicines. 2021;9(6):690.","journal-title":"Biomedicines"},{"issue":"3","key":"123_CR15","doi-asserted-by":"publisher","first-page":"296","DOI":"10.1038\/nprot.2010.184","volume":"6","author":"KD Choi","year":"2011","unstructured":"Choi KD, Vodyanik M, Slukvin II. Hematopoietic differentiation and production of mature myeloid cells from human pluripotent stem cells. Nat Protoc. 2011;6(3):296\u2013313.","journal-title":"Nat Protoc"},{"issue":"12","key":"123_CR16","doi-asserted-by":"publisher","first-page":"1282","DOI":"10.1007\/s11427-015-4967-4","volume":"58","author":"C Zeng","year":"2015","unstructured":"Zeng C, et al. Pathways related to PMA-differentiated THP1 human monocytic leukemia cells revealed by RNA-seq. Sci China Life Sci. 2015;58(12):1282\u20137.","journal-title":"Sci China Life Sci"},{"issue":"3","key":"123_CR17","doi-asserted-by":"publisher","first-page":"147","DOI":"10.1002\/(SICI)1099-1069(199609)14:3<147::AID-HON582>3.0.CO;2-3","volume":"14","author":"CS Chim","year":"1996","unstructured":"Chim CS, et al. All-trans retinoic acid (ATRA) in the treatment of acute promyelocytic leukemia (APL). Hematol Oncol. 1996;14(3):147\u201354.","journal-title":"Hematol Oncol"},{"issue":"6","key":"123_CR18","doi-asserted-by":"publisher","first-page":"3734","DOI":"10.1002\/tox.24187","volume":"39","author":"C Wu","year":"2024","unstructured":"Wu C, et al. Epigenetic activation of METTL14 promotes docetaxel resistance in prostate cancer by promoting pri-microRNA-129 maturation. Environ Toxicol. 2024;39(6):3734\u201345.","journal-title":"Environ Toxicol"},{"issue":"10","key":"123_CR19","doi-asserted-by":"publisher","first-page":"1737","DOI":"10.18632\/oncotarget.1408","volume":"4","author":"A Borodovsky","year":"2013","unstructured":"Borodovsky A, et al. 5-azacitidine reduces methylation, promotes differentiation and induces tumor regression in a patient-derived IDH1 mutant glioma xenograft. Oncotarget. 2013;4(10):1737\u201347.","journal-title":"Oncotarget"},{"issue":"3","key":"123_CR20","doi-asserted-by":"publisher","first-page":"1019","DOI":"10.7150\/jca.60381","volume":"13","author":"L Sang","year":"2022","unstructured":"Sang L, et al. The m(6)A RNA methyltransferase METTL3\/METTL14 promotes leukemogenesis through the mdm2\/p53 pathway in acute myeloid leukemia. J Cancer. 2022;13(3):1019\u201330.","journal-title":"J Cancer"},{"issue":"2","key":"123_CR21","doi-asserted-by":"publisher","first-page":"191","DOI":"10.1016\/j.stem.2017.11.016","volume":"22","author":"H Weng","year":"2018","unstructured":"Weng H, et al. METTL14 inhibits hematopoietic stem\/progenitor differentiation and promotes leukemogenesis via mRNA m(6)A modification. Cell Stem Cell. 2018;22(2):191-205 e9.","journal-title":"Cell Stem Cell"},{"issue":"7","key":"123_CR22","doi-asserted-by":"publisher","first-page":"e70771","DOI":"10.1002\/cam4.70771","volume":"14","author":"Y Tang","year":"2025","unstructured":"Tang Y, et al. METTL3, an independent adverse prognostic factor for AML, promotes the development of AML by modulating the PGC-1alpha-MAPK pathway and PGC-1alpha-antioxidant system axis. Cancer Med. 2025;14(7):e70771.","journal-title":"Cancer Med"},{"issue":"2","key":"123_CR23","doi-asserted-by":"publisher","first-page":"1993","DOI":"10.1007\/s12013-024-01610-4","volume":"83","author":"L Han","year":"2025","unstructured":"Han L, et al. METTL3\/YTDHF1 stabilizes CSRP1 mRNA to regulate glycolysis and promote acute myeloid leukemia progression. Cell Biochem Biophys. 2025;83(2):1993\u20132007.","journal-title":"Cell Biochem Biophys"},{"issue":"11","key":"123_CR24","doi-asserted-by":"publisher","first-page":"992","DOI":"10.1038\/s41419-022-05435-y","volume":"13","author":"M Li","year":"2022","unstructured":"Li M, et al. Hdac1\/3-dependent moderate liquid-liquid phase separation of YY1 promotes METTL3 expression and AML cell proliferation. Cell Death Dis. 2022;13(11):992.","journal-title":"Cell Death Dis"},{"issue":"1","key":"123_CR25","doi-asserted-by":"publisher","first-page":"59","DOI":"10.1186\/s40364-023-00495-4","volume":"11","author":"X Yang","year":"2023","unstructured":"Yang X, et al. EIF4A3-induced circ_0001187 facilitates AML suppression through promoting ubiquitin-proteasomal degradation of METTL3 and decreasing m6A modification level mediated by miR-499a-5p\/RNF113A pathway. Biomark Res. 2023;11(1):59.","journal-title":"Biomark Res"},{"issue":"1","key":"123_CR26","doi-asserted-by":"publisher","first-page":"1759","DOI":"10.1038\/s41598-022-05797-5","volume":"12","author":"F Zhong","year":"2022","unstructured":"Zhong F, et al. M6A-related lncRNAs predict prognosis and indicate immune microenvironment in acute myeloid leukemia. Sci Rep. 2022;12(1):1759.","journal-title":"Sci Rep"},{"issue":"10","key":"123_CR27","doi-asserted-by":"publisher","first-page":"1232","DOI":"10.1080\/15384101.2023.2204770","volume":"22","author":"S Wu","year":"2023","unstructured":"Wu S, et al. Mettl3 affects FLT3-ITD+ acute myeloid leukemia by mediating autophagy by regulating PSMA3-AS1 stability. Cell Cycle. 2023;22(10):1232\u201345.","journal-title":"Cell Cycle"},{"issue":"11","key":"123_CR28","doi-asserted-by":"publisher","first-page":"1369","DOI":"10.1038\/nm.4416","volume":"23","author":"LP Vu","year":"2017","unstructured":"Vu LP, et al. The N(6)-methyladenosine (m(6)A)-forming enzyme METTL3 controls myeloid differentiation of normal hematopoietic and leukemia cells. Nat Med. 2017;23(11):1369\u201376.","journal-title":"Nat Med"},{"issue":"1","key":"123_CR29","doi-asserted-by":"publisher","first-page":"74","DOI":"10.1038\/s41392-020-00450-x","volume":"6","author":"X Jiang","year":"2021","unstructured":"Jiang X, et al. The role of m6A modification in the biological functions and diseases. Signal Transduct Target Ther. 2021;6(1):74.","journal-title":"Signal Transduct Target Ther"},{"key":"123_CR30","doi-asserted-by":"publisher","first-page":"963689724128279","DOI":"10.1177\/09636897241282792","volume":"33","author":"Y Zeng","year":"2024","unstructured":"Zeng Y, et al. Regulatory Network of Methyltransferase-Like 3 in Stem Cells: Mechanisms and Medical Implications. Cell Transplant. 2024;33:9636897241282792.","journal-title":"Cell Transplant"},{"key":"123_CR31","doi-asserted-by":"publisher","first-page":"1937","DOI":"10.2147\/OTT.S191621","volume":"12","author":"J Zhang","year":"2019","unstructured":"Zhang J, Gu Y, Chen B. Mechanisms of drug resistance in acute myeloid leukemia. Onco Targets Ther. 2019;12:1937\u201345.","journal-title":"Onco Targets Ther"},{"issue":"1","key":"123_CR32","doi-asserted-by":"publisher","first-page":"233","DOI":"10.1038\/s41419-025-07560-w","volume":"16","author":"CQ Jiao","year":"2025","unstructured":"Jiao CQ, et al. Targeting METTL3 mitigates venetoclax resistance via proteasome-mediated modulation of MCL1 in acute myeloid leukemia. Cell Death Dis. 2025;16(1):233.","journal-title":"Cell Death Dis"},{"issue":"3","key":"123_CR33","first-page":"470","volume":"45","author":"X Zhang","year":"2025","unstructured":"Zhang X, et al. METTL3-mediated m(6)A modification promotes FOXO3 expression and anthracycline resistance in acute myeloid leukemia cells through autophagy regulation. Nan Fang Yi Ke Da Xue Xue Bao. 2025;45(3):470\u20138.","journal-title":"Nan Fang Yi Ke Da Xue Xue Bao"},{"issue":"11","key":"123_CR34","doi-asserted-by":"publisher","first-page":"2586","DOI":"10.1038\/s41375-022-01696-w","volume":"36","author":"M Li","year":"2022","unstructured":"Li M, et al. METTL3 mediates chemoresistance by enhancing AML homing and engraftment via ITGA4. Leukemia. 2022;36(11):2586\u201395.","journal-title":"Leukemia"},{"issue":"6","key":"123_CR35","doi-asserted-by":"publisher","first-page":"1659","DOI":"10.1002\/2211-5463.13165","volume":"11","author":"ZP Pan","year":"2021","unstructured":"Pan ZP, et al. METTL3 mediates bone marrow mesenchymal stem cell adipogenesis to promote chemoresistance in acute myeloid leukaemia. FEBS Open Bio. 2021;11(6):1659\u201372.","journal-title":"FEBS Open Bio"},{"issue":"3","key":"123_CR36","doi-asserted-by":"publisher","first-page":"298","DOI":"10.1016\/j.jgr.2023.12.003","volume":"48","author":"S Cheng","year":"2024","unstructured":"Cheng S, et al. 20(S)-ginsenoside Rh2 ameliorates ATRA resistance in APL by modulating lactylation-driven METTL3. J Ginseng Res. 2024;48(3):298\u2013309.","journal-title":"J Ginseng Res"},{"issue":"15","key":"123_CR37","doi-asserted-by":"publisher","first-page":"1933","DOI":"10.1080\/17568919.2025.2546781","volume":"17","author":"F Wu","year":"2025","unstructured":"Wu F, Yu L, Xu S. Recent advances in small molecules targeting the METTL3. Future Med Chem. 2025;17(15):1933\u201344.","journal-title":"Future Med Chem"},{"issue":"3","key":"123_CR38","doi-asserted-by":"publisher","first-page":"2981","DOI":"10.1021\/acs.jmedchem.4c02225","volume":"68","author":"G Dutheuil","year":"2025","unstructured":"Dutheuil G, et al. Discovery, optimization, and preclinical pharmacology of EP652, a METTL3 inhibitor with efficacy in liquid and solid tumor models. J Med Chem. 2025;68(3):2981\u20133003.","journal-title":"J Med Chem"},{"issue":"7","key":"123_CR39","doi-asserted-by":"publisher","first-page":"1061","DOI":"10.1021\/acsmedchemlett.1c00280","volume":"12","author":"RW Sabnis","year":"2021","unstructured":"Sabnis RW. Novel METTL3 modulators for treating acute myeloid leukemia (AML). ACS Med Chem Lett. 2021;12(7):1061\u20132.","journal-title":"ACS Med Chem Lett"},{"issue":"3","key":"123_CR40","first-page":"783","volume":"83","author":"JH Lee","year":"2022","unstructured":"Lee JH, et al. Discovery of substituted indole derivatives as allosteric inhibitors of m(6) A-RNA methyltransferase, METTL3-14 complex. Drug Dev Res. 2022;83(3):783\u201399.","journal-title":"Drug Dev Res"},{"key":"123_CR41","doi-asserted-by":"publisher","DOI":"10.3390\/ph15040440","author":"JH Lee","year":"2022","unstructured":"Lee JH, et al. Eltrombopag as an allosteric inhibitor of the METTL3-14 complex affecting the m(6)a methylation of RNA in acute myeloid leukemia cells. Pharmaceuticals (Basel). 2022. https:\/\/doi.org\/10.3390\/ph15040440.","journal-title":"Pharmaceuticals (Basel)"},{"key":"123_CR42","doi-asserted-by":"publisher","first-page":"1629864","DOI":"10.3389\/fonc.2025.1629864","volume":"15","author":"X Liu","year":"2025","unstructured":"Liu X, Kan X. Small-molecule and peptide inhibitors of m6A regulators. Front Oncol. 2025;15:1629864.","journal-title":"Front Oncol"},{"issue":"17","key":"123_CR43","doi-asserted-by":"publisher","first-page":"12738","DOI":"10.1021\/acs.jmedchem.1c00773","volume":"64","author":"A Dolbois","year":"2021","unstructured":"Dolbois A, et al. 1,4,9-triazaspiro[5.5]undecan-2-one derivatives as potent and selective METTL3 inhibitors. J Med Chem. 2021;64(17):12738\u201360.","journal-title":"J Med Chem"},{"issue":"6","key":"123_CR44","doi-asserted-by":"publisher","first-page":"460","DOI":"10.1038\/s41594-021-00606-5","volume":"28","author":"J Li","year":"2021","unstructured":"Li J, Gregory RI. Mining for METTL3 inhibitors to suppress cancer. Nat Struct Mol Biol. 2021;28(6):460\u20132.","journal-title":"Nat Struct Mol Biol"},{"issue":"19","key":"123_CR45","doi-asserted-by":"publisher","first-page":"3035","DOI":"10.1002\/cmdc.202100291","volume":"16","author":"EV Moroz-Omori","year":"2021","unstructured":"Moroz-Omori EV, et al. Mettl3 inhibitors for epitranscriptomic modulation of cellular processes. ChemMedChem. 2021;16(19):3035\u201343.","journal-title":"ChemMedChem"},{"key":"123_CR46","doi-asserted-by":"crossref","unstructured":"Justin C Moser, K.P.P., Jordi Rodon Ahnert, Yaara Ofir-Rosenfeld, and Josefin-Beate Holz, Phase 1 dose escalation and cohort expansion study evaluating safety, PK, PD and clinical activity of STC-15, a METTL-3 inhibitor, in patients with advanced malignancies. Journal of Clinical Oncology, 2024. 42(16).","DOI":"10.1200\/JCO.2024.42.16_suppl.2586"},{"key":"123_CR47","doi-asserted-by":"publisher","first-page":"116843","DOI":"10.1016\/j.ejmech.2024.116843","volume":"279","author":"K Hwang","year":"2024","unstructured":"Hwang K, et al. Targeted degradation of METTL3 against acute myeloid leukemia and gastric cancer. Eur J Med Chem. 2024;279:116843.","journal-title":"Eur J Med Chem"},{"issue":"1","key":"123_CR48","doi-asserted-by":"publisher","first-page":"177","DOI":"10.1016\/j.chembiol.2023.12.009","volume":"31","author":"W Du","year":"2024","unstructured":"Du W, et al. Discovery of a PROTAC degrader for METTL3-METTL14 complex. Cell Chem Biol. 2024;31(1):177-183 e17.","journal-title":"Cell Chem Biol"},{"issue":"4","key":"123_CR49","doi-asserted-by":"publisher","first-page":"101452","DOI":"10.1016\/j.gendis.2024.101452","volume":"12","author":"R Nar","year":"2025","unstructured":"Nar R, et al. Targeting METTL3 protein by proteolysis-targeting chimeras: a novel therapeutic approach for acute myeloid leukemia. Genes Dis. 2025;12(4):101452.","journal-title":"Genes Dis"},{"issue":"9","key":"123_CR50","doi-asserted-by":"publisher","first-page":"4194","DOI":"10.1039\/D5MD00359H","volume":"16","author":"AC Weldert","year":"2025","unstructured":"Weldert AC, et al. Structure-guided design of a methyltransferase-like 3 (METTL3) proteolysis targeting chimera (PROTAC) incorporating an indole-nicotinamide chemotype. RSC Med Chem. 2025;16(9):4194\u2013207.","journal-title":"RSC Med Chem"},{"issue":"11","key":"123_CR51","doi-asserted-by":"publisher","first-page":"2299","DOI":"10.1007\/s00044-025-03464-8","volume":"34","author":"AR Smith","year":"2025","unstructured":"Smith AR, et al. Discovery of CRBN-recruiting PROTAC degraders of the METTL3-METTL14 complex. Med Chem Res. 2025;34(11):2299\u2013308.","journal-title":"Med Chem Res"},{"issue":"14","key":"123_CR52","doi-asserted-by":"publisher","first-page":"2595","DOI":"10.7150\/ijbs.45886","volume":"16","author":"N Ding","year":"2020","unstructured":"Ding N, et al. Chidamide increases the sensitivity of non-small cell lung cancer to Crizotinib by decreasing c-MET mRNA methylation. Int J Biol Sci. 2020;16(14):2595\u2013611.","journal-title":"Int J Biol Sci"},{"key":"123_CR53","doi-asserted-by":"crossref","unstructured":"Yin, J., et al., A Phase II Trial of the Double Epigenetic Priming Regimen Including Chidamide and Decitabine for Relapsed\/Refractory Acute Myeloid Leukemia. Front Oncol, 2021. 11: p. 726926.","DOI":"10.3389\/fonc.2021.726926"},{"key":"123_CR54","doi-asserted-by":"publisher","first-page":"114268","DOI":"10.1016\/j.intimp.2025.114268","volume":"151","author":"J Yang","year":"2025","unstructured":"Yang J, et al. A phase 2 study of chidamide in combination with CAG and venetoclax-azacitidine in acute myeloid leukemia: clinical safety, efficacy, and correlative analysis. Int Immunopharmacol. 2025;151:114268.","journal-title":"Int Immunopharmacol"},{"issue":"1","key":"123_CR55","doi-asserted-by":"publisher","first-page":"2449","DOI":"10.1182\/blood-2024-209073","volume":"144","author":"L Zhang","year":"2024","unstructured":"Zhang L, Zhang HZ, Wang S, Wu X, Yang Q, Cheng Y, et al. Mettl3-mediated m6a modification is essential for the maintenance of genomic stability of erythroid cells. Blood. 2024;144(1):2449.","journal-title":"Blood"},{"key":"123_CR56","doi-asserted-by":"crossref","unstructured":"Jin Zeng, L.-T.D., Shu-Juan Xie, Zhen-Dong Xiao,, RNA modification-mediated aberrant alternative splicing: An underlying driver of disease pathogenesis. Cell Investigation,, 2025;1(4):100047.","DOI":"10.1016\/j.clnves.2025.100047"},{"issue":"1","key":"123_CR57","doi-asserted-by":"publisher","first-page":"1017","DOI":"10.1186\/s40001-025-03351-3","volume":"30","author":"F Yuan","year":"2025","unstructured":"Yuan F, et al. The role and mechanism of METTL3 in cancer: emerging insights into m6A methylation and therapeutic potential. Eur J Med Res. 2025;30(1):1017.","journal-title":"Eur J Med Res"},{"issue":"1","key":"123_CR58","doi-asserted-by":"publisher","first-page":"132","DOI":"10.1186\/s43556-025-00373-5","volume":"6","author":"C Ma","year":"2025","unstructured":"Ma C, et al. Epigenetic drugs in cancer therapy: mechanisms, immune modulation, and therapeutic applications. Mol Biomed. 2025;6(1):132.","journal-title":"Mol Biomed"},{"issue":"1","key":"123_CR59","doi-asserted-by":"publisher","first-page":"132","DOI":"10.1007\/s10565-025-10086-8","volume":"41","author":"X Fu","year":"2025","unstructured":"Fu X, Ruan X, He J. METTL3-driven m(6)A epigenetics in gastric cancer: unveiling oncogenic networks and clinical translation from tumorigenesis to therapy resistance. Cell Biol Toxicol. 2025;41(1):132.","journal-title":"Cell Biol Toxicol"},{"issue":"12","key":"123_CR60","doi-asserted-by":"publisher","first-page":"1155","DOI":"10.4155\/fmc-2020-0073","volume":"12","author":"X Liu","year":"2020","unstructured":"Liu X, et al. Assays and technologies for developing proteolysis targeting chimera degraders. Future Med Chem. 2020;12(12):1155\u201379.","journal-title":"Future Med Chem"},{"key":"123_CR61","doi-asserted-by":"publisher","first-page":"110446","DOI":"10.1016\/j.cellsig.2022.110446","volume":"99","author":"H Graham","year":"2022","unstructured":"Graham H. The mechanism of action and clinical value of PROTACs: a graphical review. Cell Signal. 2022;99:110446.","journal-title":"Cell Signal"},{"issue":"1","key":"123_CR62","doi-asserted-by":"publisher","first-page":"103","DOI":"10.1186\/s13045-020-00924-z","volume":"13","author":"Y He","year":"2020","unstructured":"He Y, et al. Proteolysis targeting chimeras (PROTACs) are emerging therapeutics for hematologic malignancies. J Hematol Oncol. 2020;13(1):103.","journal-title":"J Hematol Oncol"},{"key":"123_CR63","doi-asserted-by":"crossref","unstructured":"Rukiye Nar, Z.W., Yafang Li, Alexis Smith, Yutao Zhang, Jue Wang, Fang Yu, Sanhui Gao, Targeting METTL3 protein by proteolysis-targeting chimeras: A novel therapeutic approach for acute myeloid leukemia. Genes & Diseases, 2025. 12(5):101452.","DOI":"10.1016\/j.gendis.2024.101452"},{"issue":"2","key":"123_CR64","doi-asserted-by":"publisher","first-page":"713","DOI":"10.1021\/jacsau.4c00040","volume":"4","author":"F Errani","year":"2024","unstructured":"Errani F, et al. Proteolysis targeting chimera degraders of the METTL3-14 m(6)a-RNA methyltransferase. JACS Au. 2024;4(2):713\u201329.","journal-title":"JACS Au"},{"issue":"3","key":"123_CR65","doi-asserted-by":"publisher","first-page":"237","DOI":"10.1021\/acsmedchemlett.9b00597","volume":"11","author":"H Gao","year":"2020","unstructured":"Gao H, Sun X, Rao Y. Protac technology: opportunities and challenges. ACS Med Chem Lett. 2020;11(3):237\u201340.","journal-title":"ACS Med Chem Lett"}],"container-title":["Blood Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s44313-026-00123-8","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s44313-026-00123-8.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s44313-026-00123-8.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,30]],"date-time":"2026-01-30T15:04:08Z","timestamp":1769785448000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s44313-026-00123-8"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,1,30]]},"references-count":65,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2026,12]]}},"alternative-id":["123"],"URL":"https:\/\/doi.org\/10.1007\/s44313-026-00123-8","relation":{},"ISSN":["2287-979X","2288-0011"],"issn-type":[{"value":"2287-979X","type":"print"},{"value":"2288-0011","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,1,30]]},"assertion":[{"value":"26 August 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"11 December 2025","order":2,"name":"revised","label":"Revised","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"11 January 2026","order":3,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"30 January 2026","order":4,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"Not applicable.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"This manuscript has been read and approved by all authors for publication and is neither submitted nor under consideration for publication elsewhere.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare no competing interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"7"}}