{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,4]],"date-time":"2026-06-04T04:07:59Z","timestamp":1780546079838,"version":"3.54.1"},"reference-count":173,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2026,5,28]],"date-time":"2026-05-28T00:00:00Z","timestamp":1779926400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Among the transcriptional dependencies that sustain leukemic identity in acute myeloid leukemia (AML), the menin\u2013KMT2A chromatin complex has emerged as a central regulatory node. The scaffold protein menin, encoded by MEN1, facilitates transcriptional activation of HOX and MEIS family genes during normal hematopoietic development. In AML, this physiologic and developmentally regulated role is co-opted to sustain constitutive HOX\/MEIS-driven programs that block differentiation and maintain leukemic potential. Although dependency on menin is most clearly established in KMT2A-rearranged and NPM1-mutated AML, this vulnerability appears to arise from a shared transcriptional state characterized by persistent HOX activation rather than from any single genetic alteration. Pharmacologic disruption of the menin-KMT2A interaction collapses stemness-associated transcriptional networks, promotes myeloid differentiation, and attenuates leukemic self-renewal. Clinical activity observed with menin inhibitors provides translational validation of this dependency and establishes menin inhibition as a differentiation-based therapeutic strategy. In this review, we examine the molecular basis of menin-dependent transcriptional regulation in AML and its implications for therapeutic targeting with menin inhibitors and resistance to therapy.<\/jats:p>","DOI":"10.3390\/ijms27114886","type":"journal-article","created":{"date-parts":[[2026,6,2]],"date-time":"2026-06-02T12:45:08Z","timestamp":1780404308000},"page":"4886","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Menin Inhibition in Acute Myeloid Leukemia: Rewiring Leukemic Transcriptional Networks"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0009-0002-0086-0556","authenticated-orcid":false,"given":"Ali","family":"Tarhini","sequence":"first","affiliation":[{"name":"Department of Oncology, Mayo Clinic, Rochester, MN 55905, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Romanos","sequence":"additional","affiliation":[{"name":"Department of Medicine, Mayo Clinic, Rochester, MN 55905, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0824-3715","authenticated-orcid":false,"given":"Aref","family":"Al-Kali","sequence":"additional","affiliation":[{"name":"Division of Hematology, Department of Medicine, Mayo Clinic, Rochester, MN 55905, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5134-7336","authenticated-orcid":false,"given":"Antoine N.","family":"Saliba","sequence":"additional","affiliation":[{"name":"Division of Hematology, Department of Medicine, Mayo Clinic, Rochester, MN 55905, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,5,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"254","DOI":"10.1056\/NEJMoa041974","article-title":"Cytoplasmic Nucleophosmin in Acute Myelogenous Leukemia with a Normal Karyotype","volume":"352","author":"Falini","year":"2005","journal-title":"N. Engl. J. Med."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"2209","DOI":"10.1056\/NEJMoa1516192","article-title":"Genomic Classification and Prognosis in Acute Myeloid Leukemia","volume":"374","author":"Papaemmanuil","year":"2016","journal-title":"N. Engl. J. Med."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"989","DOI":"10.1016\/j.jmoldx.2025.06.007","article-title":"A Systematic, Evidence-Based Workflow for Classifying KMT2A Fusions in Acute Myeloid Leukemia","volume":"27","author":"Petersen","year":"2025","journal-title":"J. Mol. Diagn."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Batayneh, O., Moein, M., Naji, N.S., Patel, A., Mandava, A.R., Goodman, A., Ross, J.S., Ho, C., Marcus, C., and Zhou, Z. (2026). Characterizing KMT2A Rearrangement in Acute Myeloid Leukemia: A Comprehensive Genomic Study. Cancers, 18.","DOI":"10.3390\/cancers18010161"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1640","DOI":"10.1038\/s41375-025-02634-2","article-title":"Characteristics and outcomes of newly diagnosed acute myeloid Leukemia with KMT2A rearrangements","volume":"39","author":"Bataller","year":"2025","journal-title":"Leukemia"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"162","DOI":"10.1038\/s41408-021-00557-6","article-title":"Predictors of outcomes in adults with acute myeloid leukemia and KMT2A rearrangements","volume":"11","author":"Issa","year":"2021","journal-title":"Blood Cancer J."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"499","DOI":"10.1016\/j.ccell.2018.08.005","article-title":"Mutant NPM1 Maintains the Leukemic State through HOX Expression","volume":"34","author":"Brunetti","year":"2018","journal-title":"Cancer Cell"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"396","DOI":"10.1038\/s41698-025-01200-4","article-title":"Dysregulation of HOXA genes in acute myeloid leukemia and targeted therapy","volume":"9","author":"Huang","year":"2025","journal-title":"NPJ Precis. Oncol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"746","DOI":"10.1158\/2159-8290.CD-22-0366","article-title":"Mutant NPM1 Directly Regulates Oncogenic Transcription in Acute Myeloid Leukemia","volume":"13","author":"Uckelmann","year":"2023","journal-title":"Cancer Discov."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"617","DOI":"10.1128\/MCB.24.2.617-628.2004","article-title":"Hoxa9 and Meis1 are key targets for MLL-ENL-mediated cellular immortalization","volume":"24","author":"Zeisig","year":"2004","journal-title":"Mol. Cell. Biol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"812","DOI":"10.1111\/bjh.19508","article-title":"The Menin story in acute myeloid leukaemia\u2014The road to success","volume":"205","author":"Ganser","year":"2024","journal-title":"Br. J. Haematol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1007\/978-1-4419-1664-8_5","article-title":"The role of menin in hematopoiesis","volume":"668","author":"Maillard","year":"2009","journal-title":"Adv. Exp. Med. Biol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"8489","DOI":"10.1038\/ncomms9489","article-title":"An LSC epigenetic signature is largely mutation independent and implicates the HOXA cluster in AML pathogenesis","volume":"6","author":"Jung","year":"2015","journal-title":"Nat. Commun."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"2762","DOI":"10.1101\/gad.1602107","article-title":"Meis1 is an essential and rate-limiting regulator of MLL leukemia stem cell potential","volume":"21","author":"Wong","year":"2007","journal-title":"Genes. Dev."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1161","DOI":"10.1002\/1097-0142(197709)40:3<1161::AID-CNCR2820400327>3.0.CO;2-2","article-title":"Chromosomes and causation of human cancer and leukemia. XXVI. Binding studies in acute lymphoblastic leukemia (ALL)","volume":"40","author":"Oshimura","year":"1977","journal-title":"Cancer"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1007\/BF00291919","article-title":"A new chromosome anomaly in acute lymphoblastic leukemia (ALL)","volume":"46","author":"David","year":"1979","journal-title":"Hum. Genet."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"10735","DOI":"10.1073\/pnas.88.23.10735","article-title":"Identification of a gene, MLL, that spans the breakpoint in 11q23 translocations associated with human leukemias","volume":"88","author":"McCabe","year":"1991","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"11794","DOI":"10.1073\/pnas.89.24.11794","article-title":"Cloning of cDNAs of the MLL gene that detect DNA rearrangements and altered RNA transcripts in human leukemic cells with 11q23 translocations","volume":"89","author":"McCabe","year":"1992","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"10464","DOI":"10.1073\/pnas.89.21.10464","article-title":"The (4;11)(q21;q23) chromosome translocations in acute leukemias involve the VDJ recombinase","volume":"89","author":"Gu","year":"1992","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"505","DOI":"10.1038\/378505a0","article-title":"Altered Hox expression and segmental identity in Mll-mutant mice","volume":"378","author":"Yu","year":"1995","journal-title":"Nature"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"7884","DOI":"10.1073\/pnas.90.16.7884","article-title":"Acute mixed-lineage leukemia t(4;11)(q21;q23) generates an MLL-AF4 fusion product","volume":"90","author":"Domer","year":"1993","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1038\/ng765","article-title":"MLL translocations specify a distinct gene expression profile that distinguishes a unique leukemia","volume":"30","author":"Armstrong","year":"2002","journal-title":"Nat. Genet."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"262","DOI":"10.1182\/blood-2002-10-3221","article-title":"Gene expression signatures in MLL-rearranged T-lineage and B-precursor acute leukemias: Dominance of HOX dysregulation","volume":"102","author":"Ferrando","year":"2003","journal-title":"Blood"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"874","DOI":"10.1038\/sj.onc.1204174","article-title":"Upregulation of Meis1 and HoxA9 in acute lymphocytic leukemias with the t(4 : 11) abnormality","volume":"20","author":"Rozovskaia","year":"2001","journal-title":"Oncogene"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"5639","DOI":"10.1128\/MCB.24.13.5639-5649.2004","article-title":"Leukemia proto-oncoprotein MLL forms a SET1-like histone methyltransferase complex with menin to regulate Hox gene expression","volume":"24","author":"Yokoyama","year":"2004","journal-title":"Mol. Cell. Biol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"587","DOI":"10.1016\/S1097-2765(04)00081-4","article-title":"Menin associates with a trithorax family histone methyltransferase complex and with the hoxc8 locus","volume":"13","author":"Hughes","year":"2004","journal-title":"Mol. Cell"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1016\/j.cell.2005.09.025","article-title":"The menin tumor suppressor protein is an essential oncogenic cofactor for MLL-associated leukemogenesis","volume":"123","author":"Yokoyama","year":"2005","journal-title":"Cell"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"31742","DOI":"10.1074\/jbc.M111.258186","article-title":"Crystal structure of menin reveals binding site for mixed lineage leukemia (MLL) protein","volume":"286","author":"Murai","year":"2011","journal-title":"J. Biol. Chem."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"542","DOI":"10.1038\/nature10806","article-title":"The same pocket in menin binds both MLL and JUND but has opposite effects on transcription","volume":"482","author":"Huang","year":"2012","journal-title":"Nature"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"40690","DOI":"10.1074\/jbc.M110.172783","article-title":"Molecular basis of the mixed lineage leukemia-menin interaction: Implications for targeting mixed lineage leukemias","volume":"285","author":"Grembecka","year":"2010","journal-title":"J. Biol. Chem."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"277","DOI":"10.1038\/nchembio.773","article-title":"Menin-MLL inhibitors reverse oncogenic activity of MLL fusion proteins in leukemia","volume":"8","author":"Grembecka","year":"2012","journal-title":"Nat. Chem. Biol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1279","DOI":"10.1038\/leu.2015.6","article-title":"Epigenomic analysis of the HOX gene loci reveals mechanisms that may control canonical expression patterns in AML and normal hematopoietic cells","volume":"29","author":"Spencer","year":"2015","journal-title":"Leukemia"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1166","DOI":"10.1158\/2159-8290.CD-16-0237","article-title":"Targeting Chromatin Regulators Inhibits Leukemogenic Gene Expression in NPM1 Mutant Leukemia","volume":"6","author":"Song","year":"2016","journal-title":"Cancer Discov."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"2000","DOI":"10.1038\/sj.leu.2404808","article-title":"Pediatric acute myeloid leukemia with NPM1 mutations is characterized by a gene expression profile with dysregulated HOX gene expression distinct from MLL-rearranged leukemias","volume":"21","author":"Mullighan","year":"2007","journal-title":"Leukemia"},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Dhiman, S., Dhillon, V., and Balasubramanian, S.K. (2024). Targeting Menin in Acute Myeloid Leukemia: Therapeutic Advances and Future Directions. Cancers, 16.","DOI":"10.3390\/cancers16223743"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"394","DOI":"10.1016\/j.tibs.2013.05.005","article-title":"Menin: A scaffold protein that controls gene expression and cell signaling","volume":"38","author":"Matkar","year":"2013","journal-title":"Trends Biochem. Sci."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"4917","DOI":"10.1038\/sj.onc.1204529","article-title":"The tumor suppressor protein menin interacts with NF-kappaB proteins and inhibits NF-kappaB-mediated transactivation","volume":"20","author":"Heppner","year":"2001","journal-title":"Oncogene"},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Scacheri, P.C., Davis, S., Odom, D.T., Crawford, G.E., Perkins, S., Halawi, M.J., Agarwal, S.K., Marx, S.J., Spiegel, A.M., and Meltzer, P.S. (2006). Genome-wide analysis of menin binding provides insights into MEN1 tumorigenesis. PLoS Genet., 2.","DOI":"10.1371\/journal.pgen.0020051"},{"key":"ref_39","first-page":"1556","article-title":"Menin expression is regulated by transforming growth factor beta signaling in leukemia cells","volume":"124","author":"Zhang","year":"2011","journal-title":"Chin. Med. J."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"823","DOI":"10.1038\/nrc2253","article-title":"MLL translocations, histone modifications and leukaemia stem-cell development","volume":"7","author":"Krivtsov","year":"2007","journal-title":"Nat. Rev. Cancer"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"12000","DOI":"10.1073\/pnas.1301278110","article-title":"An MLL-dependent network sustains hematopoiesis","volume":"110","author":"Artinger","year":"2013","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"918","DOI":"10.3324\/haematol.2012.074195","article-title":"The trithorax protein partner menin acts in tandem with EZH2 to suppress C\/EBP\u03b1 and differentiation in MLL-AF9 leukemia","volume":"98","author":"Thiel","year":"2013","journal-title":"Haematologica"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"749","DOI":"10.1073\/pnas.0408836102","article-title":"Menin and MLL cooperatively regulate expression of cyclin-dependent kinase inhibitors","volume":"102","author":"Milne","year":"2005","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"6074","DOI":"10.1128\/MCB.00924-09","article-title":"Global analysis of H3K4 methylation defines MLL family member targets and points to a role for MLL1-mediated H3K4 methylation in the regulation of transcriptional initiation by RNA polymerase II","volume":"29","author":"Wang","year":"2009","journal-title":"Mol. Cell. Biol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"1018","DOI":"10.1073\/pnas.0510347103","article-title":"The tumor suppressor menin regulates hematopoiesis and myeloid transformation by influencing Hox gene expression","volume":"103","author":"Chen","year":"2006","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1817","DOI":"10.1042\/BST20210234","article-title":"Role of the HOXA cluster in HSC emergence and blood cancer","volume":"49","author":"Abuhantash","year":"2021","journal-title":"Biochem. Soc. Trans."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"388","DOI":"10.1182\/blood-2011-03-341081","article-title":"Identification and characterization of Hoxa9 binding sites in hematopoietic cells","volume":"119","author":"Huang","year":"2012","journal-title":"Blood"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"4732","DOI":"10.1182\/blood-2006-08-043356","article-title":"Evidence that the Pim1 kinase gene is a direct target of HOXA9","volume":"109","author":"Hu","year":"2007","journal-title":"Blood"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1933","DOI":"10.18632\/oncotarget.1306","article-title":"HoxA9 regulated Bcl-2 expression mediates survival of myeloid progenitors and the severity of HoxA9-dependent leukemia","volume":"4","author":"Brumatti","year":"2013","journal-title":"Oncotarget"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"3137","DOI":"10.1182\/bloodadvances.2018025866","article-title":"HoxA9 transforms murine myeloid cells by a feedback loop driving expression of key oncogenes and cell cycle control genes","volume":"2","author":"Zhong","year":"2018","journal-title":"Blood Adv."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"901","DOI":"10.1038\/leu.2014.287","article-title":"Insulin-like growth factor 1 is a direct HOXA9 target important for hematopoietic transformation","volume":"29","author":"Steger","year":"2015","journal-title":"Leukemia"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"5181","DOI":"10.1128\/MCB.00545-09","article-title":"HOXA9 modulates its oncogenic partner Meis1 to influence normal hematopoiesis","volume":"29","author":"Hu","year":"2009","journal-title":"Mol. Cell. Biol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"224","DOI":"10.1128\/MCB.21.1.224-234.2001","article-title":"Defining Roles for HOX and MEIS1 Genes in Induction of Acute Myeloid Leukemia","volume":"21","author":"Thorsteinsdottir","year":"2001","journal-title":"Mol. Cell. Biol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"1000","DOI":"10.1038\/leu.2012.356","article-title":"The role of HOX genes in normal hematopoiesis and acute leukemia","volume":"27","author":"Alharbi","year":"2013","journal-title":"Leukemia"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"3902","DOI":"10.1128\/MCB.26.10.3902-3916.2006","article-title":"Persistent Transactivation by Meis1 Replaces Hox Function in Myeloid Leukemogenesis Models: Evidence for Co-Occupancy of Meis1-Pbx and Hox-Pbx Complexes on Promoters of Leukemia-Associated Genes","volume":"26","author":"Wang","year":"2006","journal-title":"Mol. Cell. Biol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"1090","DOI":"10.1038\/onc.2015.174","article-title":"Role of HOXA9 in leukemia: Dysregulation, cofactors and essential targets","volume":"35","author":"Collins","year":"2016","journal-title":"Oncogene"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"9899","DOI":"10.1073\/pnas.1402238111","article-title":"C\/EBP\u03b1 is an essential collaborator in Hoxa9\/Meis1-mediated leukemogenesis","volume":"111","author":"Collins","year":"2014","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"649","DOI":"10.1016\/j.stem.2011.05.004","article-title":"Functional Crosstalk between Bmi1 and MLL\/Hoxa9 Axis in Establishment of Normal Hematopoietic and Leukemic Stem Cells","volume":"8","author":"Smith","year":"2011","journal-title":"Cell Stem Cell"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"13120","DOI":"10.1073\/pnas.231115398","article-title":"Meis1a suppresses differentiation by G-CSF and promotes proliferation by SCF: Potential mechanisms of cooperativity with Hoxa9 in myeloid leukemia","volume":"98","author":"Calvo","year":"2001","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"597","DOI":"10.1016\/j.ccr.2010.04.024","article-title":"GSK-3 Promotes Conditional Association of CREB and Its Coactivators with MEIS1 to Facilitate HOX-Mediated Transcription and Oncogenesis","volume":"17","author":"Wang","year":"2010","journal-title":"Cancer Cell"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1007\/978-3-031-62731-6_18","article-title":"HOXA9 Regulome and Pharmacological Interventions in Leukemia","volume":"1459","author":"Aryal","year":"2024","journal-title":"Adv. Exp. Med. Biol."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"2041","DOI":"10.1038\/leu.2008.198","article-title":"HOX expression patterns identify a common signature for favorable AML","volume":"22","author":"Andreeff","year":"2008","journal-title":"Leukemia"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"186","DOI":"10.1038\/sj.leu.2402354","article-title":"Quantitative HOX expression in chromosomally defined subsets of acute myelogenous leukemia","volume":"16","author":"Drabkin","year":"2002","journal-title":"Leukemia"},{"key":"ref_64","doi-asserted-by":"crossref","unstructured":"Xie, F., Zhang, T.J., Zhang, X.L., Xu, Z.J., Qiao, L., Wang, Y., Zhao, Y.J., Qian, J., and Zhou, J.D. (2025). Identification of HOXA9 methylation as an epigenetic biomarker predicting prognosis and guiding treatment choice in acute myeloid leukemia. BMC Cancer, 25.","DOI":"10.1186\/s12885-025-13633-y"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"2482","DOI":"10.1038\/s41375-021-01309-y","article-title":"Therapeutic implications of menin inhibition in acute leukemias","volume":"35","author":"Issa","year":"2021","journal-title":"Leukemia"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"1490","DOI":"10.1038\/leu.2009.33","article-title":"New insights to the MLL recombinome of acute leukemias","volume":"23","author":"Meyer","year":"2009","journal-title":"Leukemia"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"11367","DOI":"10.1158\/0008-5472.CAN-05-1041","article-title":"Leukemogenic MLL fusion proteins bind across a broad region of the Hox a9 locus, promoting transcription and multiple histone modifications","volume":"65","author":"Milne","year":"2005","journal-title":"Cancer Res."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"2840","DOI":"10.1038\/s41375-021-01244-y","article-title":"Tip60 activates Hoxa9 and Meis1 expression through acetylation of H2A.Z, promoting MLL-AF10 and MLL-ENL acute myeloid leukemia","volume":"35","author":"Yamagata","year":"2021","journal-title":"Leukemia"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"660","DOI":"10.1016\/j.ccell.2019.11.001","article-title":"A Menin-MLL Inhibitor Induces Specific Chromatin Changes and Eradicates Disease in Models of MLL-Rearranged Leukemia","volume":"36","author":"Krivtsov","year":"2019","journal-title":"Cancer Cell"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1097\/MOH.0000000000000123","article-title":"Mixed lineage rearranged leukaemia: Pathogenesis and targeting DOT1L","volume":"22","author":"Stein","year":"2015","journal-title":"Curr. Opin. Hematol."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"335","DOI":"10.1038\/nm.3832","article-title":"DOT1L inhibits SIRT1-mediated epigenetic silencing to maintain leukemic gene expression in MLL-rearranged leukemia","volume":"21","author":"Chen","year":"2015","journal-title":"Nat. Med."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"15751","DOI":"10.1073\/pnas.1111498108","article-title":"Function of leukemogenic mixed lineage leukemia 1 (MLL) fusion proteins through distinct partner protein complexes","volume":"108","author":"Biswas","year":"2011","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"341","DOI":"10.1101\/gad.311639.118","article-title":"Structural and functional analysis of the DOT1L-AF10 complex reveals mechanistic insights into MLL-AF10-associated leukemogenesis","volume":"32","author":"Zhang","year":"2018","journal-title":"Genes Dev."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"4514","DOI":"10.1182\/blood-2005-11-4745","article-title":"Both carboxy-terminus NES motif and mutated tryptophan(s) are crucial for aberrant nuclear export of nucleophosmin leukemic mutants in NPMc+ AML","volume":"107","author":"Falini","year":"2006","journal-title":"Blood"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"6230","DOI":"10.1158\/0008-5472.CAN-07-0273","article-title":"Born to be exported: COOH-terminal nuclear export signals of different strength ensure cytoplasmic accumulation of nucleophosmin leukemic mutants","volume":"67","author":"Bolli","year":"2007","journal-title":"Cancer Res."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"4376","DOI":"10.1038\/sj.onc.1209453","article-title":"Cytoplasmic localization of NPM in myeloid leukemias is dictated by gain-of-function mutations that create a functional nuclear export signal","volume":"25","author":"Mariano","year":"2006","journal-title":"Oncogene"},{"key":"ref_77","doi-asserted-by":"crossref","unstructured":"Arregi, I., Falces, J., Olazabal-Herrero, A., Alonso-Mari\u00f1o, M., Taneva, S.G., Rodr\u00edguez, J.A., Urbaneja, M.A., and Ba\u00f1uelos, S. (2015). Leukemia-Associated Mutations in Nucleophosmin Alter Recognition by CRM1: Molecular Basis of Aberrant Transport. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0130610"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"724","DOI":"10.1158\/2159-8290.CD-22-0424","article-title":"Mutant NPM1 Hijacks Transcriptional Hubs to Maintain Pathogenic Gene Programs in Acute Myeloid Leukemia","volume":"13","author":"Wang","year":"2023","journal-title":"Cancer Discov."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1038\/s41408-024-01004-y","article-title":"Regulation of HOX gene expression in AML","volume":"14","author":"Khan","year":"2024","journal-title":"Blood Cancer J."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"848","DOI":"10.1038\/leu.2011.277","article-title":"Downregulation of MEIS1 impairs long-term expansion of CD34+ NPM1-mutated acute myeloid leukemia cells","volume":"26","author":"Woolthuis","year":"2012","journal-title":"Leukemia"},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"1336","DOI":"10.1038\/s41375-023-01882-4","article-title":"Causal linkage of presence of mutant NPM1 to efficacy of novel therapeutic agents against AML cells with mutant NPM1","volume":"37","author":"Mill","year":"2023","journal-title":"Leukemia"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"1732","DOI":"10.1038\/s41375-023-01942-9","article-title":"NPM1 mutation reprograms leukemic transcription network via reshaping TAD topology","volume":"37","author":"Lai","year":"2023","journal-title":"Leukemia"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"764","DOI":"10.1128\/MCB.19.1.764","article-title":"CREB binding protein interacts with nucleoporin-specific FG repeats that activate transcription and mediate NUP98-HOXA9 oncogenicity","volume":"19","author":"Kasper","year":"1999","journal-title":"Mol. Cell Biol."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"16248","DOI":"10.1074\/jbc.M109.048785","article-title":"Inhibition of CRM1-mediated nuclear export of transcription factors by leukemogenic NUP98 fusion proteins","volume":"285","author":"Takeda","year":"2010","journal-title":"J. Biol. Chem."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"e09540","DOI":"10.7554\/eLife.09540","article-title":"Chromatin-prebound Crm1 recruits Nup98-HoxA9 fusion to induce aberrant expression of Hox cluster genes","volume":"5","author":"Oka","year":"2016","journal-title":"eLife"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"4247","DOI":"10.1038\/sj.onc.1205516","article-title":"Nup98-HoxA9 immortalizes myeloid progenitors, enforces expression of Hoxa9, Hoxa7 and Meis1, and alters cytokine-specific responses in a manner similar to that induced by retroviral co-expression of Hoxa9 and Meis1","volume":"21","author":"Calvo","year":"2002","journal-title":"Oncogene"},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"6281","DOI":"10.1093\/nar\/gkab473","article-title":"The H3K36me2 methyltransferase NSD1 modulates H3K27ac at active enhancers to safeguard gene expression","volume":"49","author":"Fang","year":"2021","journal-title":"Nucleic Acids Res."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"804","DOI":"10.1038\/ncb1608","article-title":"NUP98-NSD1 links H3K36 methylation to Hox-A gene activation and leukaemogenesis","volume":"9","author":"Wang","year":"2007","journal-title":"Nat. Cell Biol."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"863","DOI":"10.1016\/j.ccell.2016.10.019","article-title":"NUP98 Fusion Proteins Interact with the NSL and MLL1 Complexes to Drive Leukemogenesis","volume":"30","author":"Xu","year":"2016","journal-title":"Cancer Cell"},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"1674","DOI":"10.1038\/s41375-024-02312-9","article-title":"Combination of menin and kinase inhibitors as an effective treatment for leukemia with NUP98 translocations","volume":"38","author":"Miao","year":"2024","journal-title":"Leukemia"},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"e935","DOI":"10.1097\/HS9.0000000000000935","article-title":"The MLL-Menin Interaction is a Therapeutic Vulnerability in NUP98-rearranged AML","volume":"7","author":"Rasouli","year":"2023","journal-title":"Hemasphere"},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"894","DOI":"10.1182\/blood.2021012806","article-title":"The menin-MLL1 interaction is a molecular dependency in NUP98-rearranged AML","volume":"139","author":"Heikamp","year":"2022","journal-title":"Blood"},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"2275","DOI":"10.1182\/blood.2020007093","article-title":"Mechanistic insights and potential therapeutic approaches for NUP98-rearranged hematologic malignancies","volume":"136","author":"Michmerhuizen","year":"2020","journal-title":"Blood"},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"889","DOI":"10.1016\/j.trecan.2025.06.002","article-title":"Advances in menin inhibition in acute myeloid leukemia","volume":"11","author":"Boussi","year":"2025","journal-title":"Trends Cancer"},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"4668","DOI":"10.1182\/blood-2007-09-111872","article-title":"The recurrent SET-NUP214 fusion as a new HOXA activation mechanism in pediatric T-cell acute lymphoblastic leukemia","volume":"111","author":"Tchinda","year":"2008","journal-title":"Blood"},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"1438","DOI":"10.1172\/JCI80825","article-title":"MLL1 and DOT1L cooperate with meningioma-1 to induce acute myeloid leukemia","volume":"126","author":"Riedel","year":"2016","journal-title":"J. Clin. Investig."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1016\/j.ccr.2011.06.020","article-title":"Cell of origin in AML: Susceptibility to MN1-induced transformation is regulated by the MEIS1\/AbdB-like HOX protein complex","volume":"20","author":"Heuser","year":"2011","journal-title":"Cancer Cell"},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"1405","DOI":"10.1038\/s41375-021-01146-z","article-title":"Menin is necessary for long term maintenance of meningioma-1 driven leukemia","volume":"35","author":"Libbrecht","year":"2021","journal-title":"Leukemia"},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"619","DOI":"10.1182\/blood.2023021359","article-title":"Acute myeloid leukemias with UBTF tandem duplications are sensitive to menin inhibitors","volume":"143","author":"Barajas","year":"2024","journal-title":"Blood"},{"key":"ref_100","first-page":"2459","article-title":"UBTF tandem duplications in pediatric myelodysplastic syndrome and acute myeloid leukemia: Implications for clinical screening and diagnosis","volume":"109","author":"Barajas","year":"2024","journal-title":"Haematologica"},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"1017","DOI":"10.1038\/ncb1464","article-title":"Leukaemic transformation by CALM-AF10 involves upregulation of Hoxa5 by hDOT1L","volume":"8","author":"Okada","year":"2006","journal-title":"Nat. Cell Biol."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"423","DOI":"10.1038\/leu.2014.221","article-title":"A critical role for CRM1 in regulating HOXA gene transcription in CALM-AF10 leukemias","volume":"29","author":"Conway","year":"2015","journal-title":"Leukemia"},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"5527","DOI":"10.1182\/bloodadvances.2020003490","article-title":"MOZ is critical for the development of MOZ\/MLL fusion-induced leukemia through regulation of Hoxa9\/Meis1 expression","volume":"6","author":"Katsumoto","year":"2022","journal-title":"Blood Adv."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1007\/s12185-013-1466-x","article-title":"Bromodomain-PHD finger protein 1 is critical for leukemogenesis associated with MOZ-TIF2 fusion","volume":"99","author":"Shima","year":"2014","journal-title":"Int. J. Hematol."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"146","DOI":"10.1158\/2159-8290.CD-22-0416","article-title":"A Molecular Switch between Mammalian MLL Complexes Dictates Response to Menin-MLL Inhibition","volume":"13","author":"Perner","year":"2023","journal-title":"Cancer Discov."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"584","DOI":"10.1182\/blood.2025029712","article-title":"Menin inhibition enhances graft-versus-leukemia effects by T-cell activation and endogenous retrovirus induction in AML","volume":"147","author":"Fetsch","year":"2026","journal-title":"Blood"},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"586","DOI":"10.1126\/science.aax5863","article-title":"Therapeutic targeting of preleukemia cells in a mouse model of NPM1 mutant acute myeloid leukemia","volume":"367","author":"Uckelmann","year":"2020","journal-title":"Science"},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"981","DOI":"10.1172\/JCI129126","article-title":"Menin inhibitor MI-3454 induces remission in MLL1-rearranged and NPM1-mutated models of leukemia","volume":"130","author":"Klossowski","year":"2020","journal-title":"J. Clin. Investig."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1182\/blood-2020-134942","article-title":"Preliminary Data on a Phase 1\/2A First in Human Study of the Menin-KMT2A (MLL) Inhibitor KO-539 in Patients with Relapsed or Refractory Acute Myeloid Leukemia","volume":"136","author":"Wang","year":"2020","journal-title":"Blood"},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"920","DOI":"10.1038\/s41586-023-05812-3","article-title":"The menin inhibitor revumenib in KMT2A-rearranged or NPM1-mutant leukaemia","volume":"615","author":"Issa","year":"2023","journal-title":"Nature"},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"e19161da","DOI":"10.1097\/01.HS9.0000968924.19161.da","article-title":"P504: Updated data for ziftomenib in patients with NPM1-mutated relapsed or refractory acute myeloid leukemia","volume":"7","author":"Fathi","year":"2023","journal-title":"HemaSphere"},{"key":"ref_112","unstructured":"(2026, February 28). FDA Approves Revumenib for Relapsed or Refractory Acute Leukemia with a KMT2A Translocation, Available online: https:\/\/www.fda.gov\/drugs\/resources-information-approved-drugs\/fda-approves-revumenib-relapsed-or-refractory-acute-leukemia-kmt2a-translocation."},{"key":"ref_113","unstructured":"(2026, February 28). FDA Approves Ziftomenib for Relapsed or Refractory Acute Myeloid Leukemia with a NPM1 Mutation, Available online: https:\/\/www.fda.gov\/drugs\/resources-information-approved-drugs\/fda-approves-ziftomenib-relapsed-or-refractory-acute-myeloid-leukemia-npm1-mutation."},{"key":"ref_114","unstructured":"(2026, February 28). FDA Approves Revumenib for Relapsed or Refractory Acute Myeloid Leukemia with a Susceptible NPM1 Mutation, Available online: https:\/\/www.fda.gov\/drugs\/resources-information-approved-drugs\/fda-approves-revumenib-relapsed-or-refractory-acute-myeloid-leukemia-susceptible-npm1-mutation."},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1200\/JCO.24.00826","article-title":"Menin Inhibition with Revumenib for KMT2A-Rearranged Relapsed or Refractory Acute Leukemia (AUGMENT-101)","volume":"43","author":"Issa","year":"2025","journal-title":"J. Clin. Oncol."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1182\/blood-2024-194384","article-title":"Updated Results and Longer Follow-up from the AUGMENT-101 Phase 2 Study of Revumenib in All Patients with Relapsed or Refractory (R\/R) KMT2Ar Acute Leukemia","volume":"144","author":"Aldoss","year":"2024","journal-title":"Blood"},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"1065","DOI":"10.1182\/blood.2025028357","article-title":"Menin inhibition with revumenib for NPM1-mutated relapsed or refractory acute myeloid leukemia: The AUGMENT-101 study","volume":"146","author":"Arellano","year":"2025","journal-title":"Blood"},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"1310","DOI":"10.1016\/S1470-2045(24)00386-3","article-title":"Ziftomenib in relapsed or refractory acute myeloid leukaemia (KOMET-001): A multicentre, open-label, multi-cohort, phase 1 trial","volume":"25","author":"Wang","year":"2024","journal-title":"Lancet Oncol."},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"6506","DOI":"10.1200\/JCO.2025.43.16_suppl.6506","article-title":"Ziftomenib in relapsed\/refractory (R\/R) NPM1-mutant acute myeloid leukemia (AML): Phase 1b\/2 clinical activity and safety results from the pivotal KOMET-001 study","volume":"43","author":"Wang","year":"2025","journal-title":"J. Clin. Oncol."},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"212","DOI":"10.1182\/blood-2024-207106","article-title":"Bleximenib Dose Optimization and Determination of RP2D from a Phase 1 Study in Relapsed\/Refractory Acute Leukemia Patients with KMT2A and NPM1 Alterations","volume":"144","author":"Searle","year":"2024","journal-title":"Blood"},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"212","DOI":"10.1182\/blood-2024-194827","article-title":"Phase 1 Results: First-in-Human Phase 1\/2 Study of the Menin-MLL Inhibitor Enzomenib (DSP-5336) in Patients with Relapsed or Refractory Acute Leukemia","volume":"144","author":"Zeidner","year":"2024","journal-title":"Blood"},{"key":"ref_122","unstructured":"Pharmaceuticals, S. (2026, March 08). REVUFORJ (Revumenib) Tablets: Full Prescribing Information. Available online: https:\/\/cms.syndax.com\/wp-content\/uploads\/Revuforj-full-prescribing-info.pdf."},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"3381","DOI":"10.1200\/JCO-25-01694","article-title":"Ziftomenib in Relapsed or Refractory NPM1-Mutated AML","volume":"43","author":"Wang","year":"2025","journal-title":"J. Clin. Oncol."},{"key":"ref_124","unstructured":"(2026, March 10). KOMZIFTI (Ziftomenib) Prescribing Information. Available online: https:\/\/kuraoncology.com\/wp-content\/uploads\/prescribinginformation.pdf."},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"1206","DOI":"10.1182\/blood.2023022480","article-title":"Preclinical efficacy of the potent, selective menin-KMT2A inhibitor JNJ-75276617 (bleximenib) in KMT2A- and NPM1-altered leukemias","volume":"144","author":"Kwon","year":"2024","journal-title":"Blood"},{"key":"ref_126","first-page":"1278","article-title":"Bleximenib, the novel menin-KMT2A inhibitor JNJ-75276617, impairs long-term proliferation and immune evasion in acute myeloid leukemia","volume":"110","author":"Hogeling","year":"2025","journal-title":"Haematologica"},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"2916","DOI":"10.1182\/blood-2023-173149","article-title":"Covalent Menin Inhibitor Bmf-219 in Patients with Relapsed or Refractory (R\/R) Acute Leukemia (AL): Preliminary Phase 1 Data from the Covalent-101 Study","volume":"142","author":"Lancet","year":"2023","journal-title":"Blood"},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"2879","DOI":"10.1182\/blood-2024-198959","article-title":"A First-in-Human Phase 1\/2 Study of the Menin-KMT2A(MLL1) Inhibitor BN104 in Adult Patients with Relapsed or Refractory Acute Leukemia","volume":"144","author":"Wu","year":"2024","journal-title":"Blood"},{"key":"ref_129","first-page":"S130","article-title":"The novel menin inhibitor ZE63-0302 has an impressive safety profile and unique chemistry that suggests improved efficacy against resistance mutations","volume":"422","author":"Hertlein","year":"2024","journal-title":"EHA Libr."},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"2113","DOI":"10.1158\/1538-7445.AM2024-2113","article-title":"Abstract 2113: HMPL-506, a novel, highly potent and differentiated menin-MLL inhibitor for the treatment of MLL-rearrangedand NPM1mutant acute leukemia in preclinical models","volume":"84","author":"Cheng","year":"2024","journal-title":"Cancer Res."},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1186\/s12935-023-02877-y","article-title":"A novel Menin-MLL1 inhibitor, DS-1594a, prevents the progression of acute leukemia with rearranged MLL1 or mutated NPM1","volume":"23","author":"Numata","year":"2023","journal-title":"Cancer Cell Int."},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"1419","DOI":"10.1158\/1538-7445.AM2025-1419","article-title":"Abstract 1419: RCZY-711, a novel, highly potent, and orally bioavailable menin-MLL inhibitor with superior efficacy in preclinical acute leukemia models","volume":"85","author":"Chen","year":"2025","journal-title":"Cancer Res."},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"1752","DOI":"10.1158\/1538-7445.AM2025-1752","article-title":"Abstract 1752: SY-13380, a novel menin-MLL inhibitor, exhibits efficacy against resistant mutations and anti-tumor activity for MLL-rearranged and NPM1-mutant acute myeloid leukemia in pre-clinical models","volume":"85","author":"Li","year":"2025","journal-title":"Cancer Res."},{"key":"ref_134","doi-asserted-by":"crossref","first-page":"107777","DOI":"10.1016\/j.jbc.2024.107777","article-title":"Drug-resistant menin variants retain high binding affinity and interactions with MLL1","volume":"300","author":"Ray","year":"2024","journal-title":"J. Biol. Chem."},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"913","DOI":"10.1038\/s41586-023-05755-9","article-title":"MEN1 mutations mediate clinical resistance to menin inhibition","volume":"615","author":"Perner","year":"2023","journal-title":"Nature"},{"key":"ref_136","doi-asserted-by":"crossref","first-page":"724","DOI":"10.1182\/blood-2024-208887","article-title":"Discerning the Landscape of Menin Inhibitor Resistance","volume":"144","author":"Bourgeois","year":"2024","journal-title":"Blood"},{"key":"ref_137","doi-asserted-by":"crossref","first-page":"e6233123","DOI":"10.1097\/01.HS9.0000967412.62331.23","article-title":"S125: Non-genetic resistance to menin inhibition in AML is reversible by perturbation of KAT6A","volume":"7","author":"Perner","year":"2023","journal-title":"HemaSphere"},{"key":"ref_138","doi-asserted-by":"crossref","first-page":"587","DOI":"10.1182\/blood-2023-185353","article-title":"Decoding the Epigenetic Drivers of Menin-MLL Inhibitor Resistance in KMT2A-Rearranged Acute Myeloid Leukemia","volume":"142","author":"Zhou","year":"2023","journal-title":"Blood"},{"key":"ref_139","doi-asserted-by":"crossref","first-page":"114901","DOI":"10.1016\/j.celrep.2024.114901","article-title":"NUP98 fusion proteins and KMT2A-MENIN antagonize PRC1.1 to drive gene expression in AML","volume":"43","author":"Heikamp","year":"2024","journal-title":"Cell Rep."},{"key":"ref_140","doi-asserted-by":"crossref","first-page":"2018","DOI":"10.1182\/blood.2023023644","article-title":"Epigenetic regulation of noncanonical menin targets modulates menin inhibitor response in acute myeloid leukemia","volume":"144","author":"Zhou","year":"2024","journal-title":"Blood"},{"key":"ref_141","doi-asserted-by":"crossref","first-page":"e83004","DOI":"10.7554\/eLife.83004","article-title":"Polycomb repressive complex 1.1 coordinates homeostatic and emergency myelopoiesis","volume":"12","author":"Oshima","year":"2023","journal-title":"eLife"},{"key":"ref_142","first-page":"3169","article-title":"BCOR and BCORL1 mutations in myelodysplastic syndromes and related disorders","volume":"122","author":"Damm","year":"2013","journal-title":"Blood J. Am. Soc. Hematol."},{"key":"ref_143","doi-asserted-by":"crossref","first-page":"2117","DOI":"10.1158\/2159-8290.CD-24-1517","article-title":"Catalytic Inhibition of KAT6\/KAT7 Enhances the Efficacy and Overcomes Primary and Acquired Resistance to Menin Inhibitors in MLL Leukemia","volume":"15","author":"Gordon","year":"2025","journal-title":"Cancer Discov."},{"key":"ref_144","doi-asserted-by":"crossref","first-page":"105268","DOI":"10.1016\/j.exphem.2025.105268","article-title":"Upfront menin-inhibitor resistance in multiply pretreated leukemias","volume":"153","author":"Mahdavi","year":"2026","journal-title":"Exp. Hematol."},{"key":"ref_145","doi-asserted-by":"crossref","unstructured":"Alati, C., Molica, M., Pitea, M., Marafioti, V., Porto, G., Policastro, G., Bilardi, E., Utano, G., Giordano, L., and Sgarlata, A. (2026). Menin Inhibition in Acute Myeloid MLL Rearranged Leukemias: A New Target for Precision Care. Cancers, 18.","DOI":"10.3390\/cancers18040637"},{"key":"ref_146","doi-asserted-by":"crossref","first-page":"3470","DOI":"10.1182\/blood-2025-3470","article-title":"TP53 inactivation confers resistance to the menin inhibitor revumenib in Acute Myeloid Leukemia","volume":"146","author":"Leung","year":"2025","journal-title":"Blood"},{"key":"ref_147","doi-asserted-by":"crossref","unstructured":"Chin, K.K., Abdul-Hay, M., Shukla, M., Geyer, M.B., Tamari, R., Ko, K.H., Xiao, W., Stein, E.M., and Cai, S.F. (2026). Overcoming MEN1-mediated resistance with menin inhibitor switching in KMT2A-rearranged acute myeloid leukemia. Leukemia.","DOI":"10.52843\/cassyni.562cnx"},{"key":"ref_148","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1038\/s41408-023-00826-6","article-title":"Targeting of epigenetic co-dependencies enhances anti-AML efficacy of Menin inhibitor in AML with MLL1-r or mutant NPM1","volume":"13","author":"Fiskus","year":"2023","journal-title":"Blood Cancer J."},{"key":"ref_149","doi-asserted-by":"crossref","first-page":"2606","DOI":"10.1200\/JCO-25-00914","article-title":"Azacitidine, Venetoclax, and Revumenib for Newly Diagnosed NPM1-Mutated or KMT2A-Rearranged AML","volume":"43","author":"Zeidner","year":"2025","journal-title":"J. Clin. Oncol."},{"key":"ref_150","first-page":"e104","article-title":"Safety and activity of revumenib in combination with fludarabine\/cytarabine (FLA) in patients with relapsed\/refractory acute leukemias","volume":"8","author":"Shukla","year":"2024","journal-title":"HemaSphere"},{"key":"ref_151","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1182\/blood-2025-47","article-title":"Phase II Study of the all-oral combination of revumenib (SNDX-5613) with decitabine\/cedazuridine (ASTX727) and venetoclax (SAVE) in newly diagnosed AML","volume":"146","author":"Jen","year":"2025","journal-title":"Blood"},{"key":"ref_152","doi-asserted-by":"crossref","first-page":"216","DOI":"10.1182\/blood-2024-204375","article-title":"Phase I\/II Study of the All-Oral Combination of Revumenib (SNDX-5613) with Decitabine\/Cedazuridine (ASTX727) and Venetoclax (SAVE) in R\/R AML","volume":"144","author":"Issa","year":"2024","journal-title":"Blood"},{"key":"ref_153","doi-asserted-by":"crossref","first-page":"5206","DOI":"10.1182\/blood-2025-5206","article-title":"Revumenib in combination with intensive induction and consolidation for newly diagnosed patients with NPM1-mutated or KMT2A-rearranged Acute Myeloid Leukemia: Preliminary results from the Phase 1b etctn 10596 study","volume":"146","author":"Mims","year":"2025","journal-title":"Blood"},{"key":"ref_154","doi-asserted-by":"crossref","first-page":"S452","DOI":"10.1016\/S2152-2650(25)01717-3","article-title":"AML-732: Ziftomenib Combined With Intensive Induction Chemotherapy (7+ 3) in Newly Diagnosed NPM1-m or KMT2A-r Acute Myeloid Leukemia (AML): Updated Phase 1a\/b Results From KOMET-007","volume":"25","author":"Zeidan","year":"2025","journal-title":"Clin. Lymphoma Myeloma Leuk."},{"key":"ref_155","doi-asserted-by":"crossref","first-page":"766","DOI":"10.1182\/blood-2025-766","article-title":"Ziftomenib in combination with venetoclax and azacitidine in newly diagnosed NPM1-m acute myeloid leukemia: Phase 1b results from KOMET-007","volume":"146","author":"Roboz","year":"2025","journal-title":"Blood"},{"key":"ref_156","doi-asserted-by":"crossref","first-page":"764","DOI":"10.1182\/blood-2025-764","article-title":"Ziftomenib in combination with venetoclax and azacitidine in relapsed\/refractory NPM1-m or KMT2A-r acute myeloid leukemia: Updated phase 1a\/b safety and clinical activity results from KOMET-007","volume":"146","author":"Issa","year":"2025","journal-title":"Blood"},{"key":"ref_157","doi-asserted-by":"crossref","first-page":"1553","DOI":"10.1182\/blood-2023-190475","article-title":"Komet-008: A Phase 1 Study to Determine the Safety and Tolerability of Ziftomenib Combinations for the Treatment of KMT2A-Rearranged or NPM1-Mutant Relapsed\/Refractory Acute Myeloid Leukemia","volume":"142","author":"Goldberg","year":"2023","journal-title":"Blood"},{"key":"ref_158","doi-asserted-by":"crossref","first-page":"5199","DOI":"10.1182\/blood-2025-5199","article-title":"Bleximenib in combination with intensive chemotherapy: A phase 1b study in newly diagnosed Acute Myeloid Leukemia with KMT2A or NPM1 alterations","volume":"146","author":"Schuh","year":"2025","journal-title":"Blood"},{"key":"ref_159","doi-asserted-by":"crossref","first-page":"S423","DOI":"10.1016\/S2152-2650(25)01665-9","article-title":"AML-418: Recommended phase 2 dose (RP2D) determination of bleximenib in combination with venetoclax+azacitidine (VEN+AZA): Phase Ib study in Newly Diagnosed (ND) and relapsed\/refractory (R\/R) acute myeloid leukemia (AML) with KMT2A or NPM1 alterations","volume":"25","author":"Wei","year":"2025","journal-title":"Clin. Lymphoma Myeloma Leuk."},{"key":"ref_160","doi-asserted-by":"crossref","first-page":"5200","DOI":"10.1182\/blood-2025-5200","article-title":"Phase 1b study of bleximenib in combination with venetoclax in Acute Myeloid Leukemia with KMT2A or NPM1 alterations","volume":"146","author":"Wei","year":"2025","journal-title":"Blood"},{"key":"ref_161","doi-asserted-by":"crossref","first-page":"765","DOI":"10.1182\/blood-2025-765","article-title":"Preliminary data from the ongoing Phase 1 study of the menin-MLL inhibitor enzomenib (DSP-5336) in combination with venetoclax and azacitidine in patients with relapsed or refractory Acute Myeloid Leukemia","volume":"146","author":"Watts","year":"2025","journal-title":"Blood"},{"key":"ref_162","doi-asserted-by":"crossref","first-page":"1106","DOI":"10.1158\/2159-8290.CD-16-0313","article-title":"Efficacy and biological correlates of response in a phase II study of venetoclax monotherapy in patients with acute myelogenous leukemia","volume":"6","author":"Konopleva","year":"2016","journal-title":"Cancer Discov."},{"key":"ref_163","doi-asserted-by":"crossref","first-page":"3371","DOI":"10.1158\/1078-0432.CCR-19-1900","article-title":"5-Azacitidine Induces NOXA to Prime AML Cells for Venetoclax-Mediated Apoptosis","volume":"26","author":"Jin","year":"2020","journal-title":"Clin. Cancer Res."},{"key":"ref_164","doi-asserted-by":"crossref","first-page":"4326","DOI":"10.1182\/bloodadvances.2019000937","article-title":"Venetoclax for AML: Changing the treatment paradigm","volume":"3","author":"Pollyea","year":"2019","journal-title":"Blood Adv."},{"key":"ref_165","doi-asserted-by":"crossref","first-page":"1637","DOI":"10.1182\/blood.2021011917","article-title":"Menin inhibition decreases Bcl-2 and synergizes with venetoclax in NPM1\/FLT3-mutated AML","volume":"138","author":"Carter","year":"2021","journal-title":"Blood"},{"key":"ref_166","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1038\/s41408-021-00603-3","article-title":"Effective Menin inhibitor-based combinations against AML with MLL rearrangement or NPM1 mutation (NPM1c)","volume":"12","author":"Fiskus","year":"2022","journal-title":"Blood Cancer J."},{"key":"ref_167","doi-asserted-by":"crossref","first-page":"2837","DOI":"10.3324\/haematol.2022.282160","article-title":"Menin inhibitor ziftomenib (KO-539) synergizes with drugs targeting chromatin regulation or apoptosis and sensitizes acute myeloid leukemia with MLL rearrangement or NPM1 mutation to venetoclax","volume":"108","author":"Rausch","year":"2023","journal-title":"Haematologica"},{"key":"ref_168","doi-asserted-by":"crossref","first-page":"3429","DOI":"10.1182\/blood-2025-3429","article-title":"Camelot-2: A phase 3 randomized, double-blind, placebo-controlled, study of bleximenib, venetoclax and azacitidine for the treatment of participants with newly diagnosed Acute Myeloid Leukemia harboring KMT2A rearrangements or NPM1 mutations, who are ineligible for intensive chemotherapy","volume":"146","author":"Jabbour","year":"2025","journal-title":"Blood"},{"key":"ref_169","doi-asserted-by":"crossref","first-page":"1654","DOI":"10.1182\/blood-2025-1654","article-title":"Bleximenib or placebo in combination with standard induction and consolidation therapy followed by maintenance for the treatment of patients with newly diagnosed KMT2A-rearranged or NPM1-mutant Acute Myeloid Leukemia eligible for intensive chemotherapy: A double-blind Phase 3 study (HOVON 181 AML\/AMLSG 37-25)","volume":"146","author":"Raaijmakers","year":"2025","journal-title":"Blood"},{"key":"ref_170","doi-asserted-by":"crossref","unstructured":"Batayneh, O., Moein, M., Goodman, A., Desai, D., Pavlick, D., Marcus, C., Ho, C., Madison, R., Huang, R.S.P., and Ross, J.S. (2025). A Comprehensive Genomic Analysis of Nucleophosmin (NPM1) in Acute Myeloid Leukemia. Cancers, 17.","DOI":"10.3390\/cancers17162710"},{"key":"ref_171","doi-asserted-by":"crossref","first-page":"2442","DOI":"10.1182\/blood.2020005037","article-title":"Synergistic targeting of FLT3 mutations in AML via combined menin-MLL and FLT3 inhibition","volume":"136","author":"Dzama","year":"2020","journal-title":"Blood"},{"key":"ref_172","doi-asserted-by":"crossref","first-page":"2958","DOI":"10.1182\/blood.2020006575","article-title":"Combinatorial treatment with menin and FLT3 inhibitors induces complete remission in AML models with activating FLT3 mutations","volume":"136","author":"Miao","year":"2020","journal-title":"Blood"},{"key":"ref_173","doi-asserted-by":"crossref","first-page":"5946","DOI":"10.1182\/blood-2022-168834","article-title":"Combination of Menin and IDH Mutant Inhibition in Acute Myeloid Leukemia","volume":"140","author":"Yoon","year":"2022","journal-title":"Blood"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/11\/4886\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,4]],"date-time":"2026-06-04T03:38:16Z","timestamp":1780544296000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/11\/4886"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,5,28]]},"references-count":173,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2026,6]]}},"alternative-id":["ijms27114886"],"URL":"https:\/\/doi.org\/10.3390\/ijms27114886","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,5,28]]}}}