{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T03:20:21Z","timestamp":1790911221092,"version":"4.1.0"},"reference-count":94,"publisher":"MDPI AG","issue":"22","license":[{"start":{"date-parts":[[2024,11,6]],"date-time":"2024-11-06T00:00:00Z","timestamp":1730851200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Germline mutations in the MEN1 gene encoding menin protein cause multiple endocrine neoplasia type 1 (MEN1) syndrome. Recent evidence suggests that inhibiting the interaction of menin with its crucial oncogenic protein partners represents a promising therapeutic strategy to AML. Menin plays a critical role in lysine methyltransferase 2A (KMT2A)-gene-rearranged and NPM1-m acute leukemias, both associated with adverse outcomes with current standard therapies, especially in the relapsed\/refractory setting. Disrupting the menin\u2013KMT2A interaction affects the proleukemogenic HOX\/MEIS transcription program. This disruption leads to the differentiation of KMT2Ar and NPM1-m AML cells. Small molecular inhibitors of the menin\u2013KMT2A interaction target the central cavity of MEN1 to inhibit the MEN1-KMT2A interaction and could target a similar transcriptional dependency in other leukemia subsets, broadening their therapeutic potential. These agents, both as monotherapies and in combination with synergistic drugs, are undergoing preclinical and clinical evaluation with promising early results. With the growing literature around menin inhibitors in AML, we discussed the biology of menin, its mechanism of action, its interacting partners in leukemia, possible inhibitors, their implications, synergistic drugs, and future therapeutic strategies in this review.<\/jats:p>","DOI":"10.3390\/cancers16223743","type":"journal-article","created":{"date-parts":[[2024,11,6]],"date-time":"2024-11-06T04:03:24Z","timestamp":1730865804000},"page":"3743","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["Targeting Menin in Acute Myeloid Leukemia: Therapeutic Advances and Future Directions"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9233-4750","authenticated-orcid":false,"given":"Sandhya","family":"Dhiman","sequence":"first","affiliation":[{"name":"Department of Oncology, Karmanos Cancer Center, School of Medicine, Wayne State University, Detroit, MI 48201, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vikram","family":"Dhillon","sequence":"additional","affiliation":[{"name":"Department of Oncology, Karmanos Cancer Center, School of Medicine, Wayne State University, Detroit, MI 48201, USA"},{"name":"Department of Oncology, Neal Cancer Center, Houston Methodist Hospital, Houston, TX 77030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9044-1309","authenticated-orcid":false,"given":"Suresh Kumar","family":"Balasubramanian","sequence":"additional","affiliation":[{"name":"Department of Oncology, Karmanos Cancer Center, School of Medicine, Wayne State University, Detroit, MI 48201, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,11,6]]},"reference":[{"key":"ref_1","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_2","doi-asserted-by":"crossref","first-page":"90614","DOI":"10.18632\/oncotarget.21598","article-title":"Targeting multiple nodes of MLL complexes to improve leukemia therapy","volume":"8","author":"Dafflon","year":"2017","journal-title":"Oncotarget"},{"key":"ref_3","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_4","doi-asserted-by":"crossref","first-page":"1617","DOI":"10.1002\/ange.201711828","article-title":"Design of the first-in-class, highly potent irreversible inhibitor targeting the menin-MLL protein\u2013protein interaction","volume":"130","author":"Xu","year":"2018","journal-title":"Angew. Chem."},{"key":"ref_5","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_6","first-page":"4461","article-title":"Structural insights into inhibition of the bivalent menin-MLL interaction by small molecules in leukemia","volume":"120","author":"Shi","year":"2012","journal-title":"Blood J. Am. Soc. Hematol."},{"key":"ref_7","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_8","doi-asserted-by":"crossref","first-page":"592","DOI":"10.1007\/s003359901051","article-title":"Isolation, genomic organization, and expression analysis of Men1, the murine homolog of the MEN1 gene","volume":"10","author":"Guru","year":"1999","journal-title":"Mamm. Genome"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"753","DOI":"10.1210\/jc.2018-01170","article-title":"UMD-MEN1 database: An overview of the 370 MEN1 variants present in 1676 patients from the French population","volume":"104","author":"Romanet","year":"2019","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"2359","DOI":"10.1016\/j.celrep.2017.02.025","article-title":"Enhancer-mediated oncogenic function of the menin tumor suppressor in breast cancer","volume":"18","author":"Dreijerink","year":"2017","journal-title":"Cell Rep."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1038\/s41388-021-02039-2","article-title":"Menin inhibition suppresses castration-resistant prostate cancer and enhances chemosensitivity","volume":"41","author":"Cherif","year":"2022","journal-title":"Oncogene"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"426","DOI":"10.1016\/j.ando.2008.06.001","article-title":"Menin regulates endocrine diseases by controlling histone modification and gene transcription","volume":"69","author":"Gao","year":"2008","journal-title":"Ann. d\u2019Endocrinol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"321","DOI":"10.1111\/febs.16268","article-title":"Molecular regulators of HOXA9 in acute myeloid leukemia","volume":"290","author":"Aryal","year":"2023","journal-title":"FEBS J."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"333","DOI":"10.1507\/endocrj.51.333","article-title":"JunD-menin interaction regulates c-Jun-mediated AP-1 transactivation","volume":"51","author":"Ikeo","year":"2004","journal-title":"Endocr. J."},{"key":"ref_15","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_16","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1186\/s13045-020-00990-3","article-title":"Targeting the Wnt\/\u03b2-catenin signaling pathway in cancer","volume":"13","author":"Zhang","year":"2020","journal-title":"J. Hematol. Oncol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1592","DOI":"10.1038\/s41594-023-01087-4","article-title":"CRISPR\u2013ChIP reveals selective regulation of H3K79me2 by Menin in MLL leukemia","volume":"30","author":"Gilan","year":"2023","journal-title":"Nat. Struct. Mol. Biol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"2351","DOI":"10.1038\/s41375-022-01666-2","article-title":"Current status and future perspectives in targeted therapy of NPM1-mutated AML","volume":"36","author":"Ranieri","year":"2022","journal-title":"Leukemia"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"691","DOI":"10.1016\/0092-8674(92)90602-9","article-title":"Involvement of a homolog of Drosophila trithorax by 11q23 chromosomal translocations in acute leukemias","volume":"71","author":"Tkachuk","year":"1992","journal-title":"Cell"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"500","DOI":"10.1016\/j.molmed.2004.08.005","article-title":"MLL: A histone methyltransferase disrupted in leukemia","volume":"10","author":"Hess","year":"2004","journal-title":"Trends Mol. Med."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"283","DOI":"10.1146\/annurev-pathol-011811-132434","article-title":"The pathogenesis of mixed-lineage leukemia","volume":"7","author":"Muntean","year":"2012","journal-title":"Annu. Rev. Pathol. Mech. Dis."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"3537","DOI":"10.1038\/sj.onc.1209400","article-title":"Tumor suppressor menin: The essential role of nuclear localization signal domains in coordinating gene expression","volume":"25","author":"La","year":"2006","journal-title":"Oncogene"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"3837","DOI":"10.1073\/pnas.061358098","article-title":"Inactivation of menin, a Smad3-interacting protein, blocks transforming growth factor type \u03b2 signaling","volume":"98","author":"Kaji","year":"2001","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s13148-019-0723-0","article-title":"Co-inhibition of HDAC and MLL-menin interaction targets MLL-rearranged acute myeloid leukemia cells via disruption of DNA damage checkpoint and DNA repair","volume":"11","author":"Ye","year":"2019","journal-title":"Clin. Epigenetics"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"5477","DOI":"10.1128\/MCB.00335-09","article-title":"Nuclear-cytoplasmic shuttling of menin regulates nuclear translocation of \u03b2-catenin","volume":"29","author":"Cao","year":"2009","journal-title":"Mol. Cell. Biol."},{"key":"ref_26","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_27","doi-asserted-by":"crossref","first-page":"983","DOI":"10.1038\/nrm2298","article-title":"Multivalent engagement of chromatin modifications by linked binding modules","volume":"8","author":"Ruthenburg","year":"2007","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_28","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_29","doi-asserted-by":"crossref","first-page":"17603","DOI":"10.1073\/pnas.1208807109","article-title":"Global identification of MLL2-targeted loci reveals MLL2\u2019s role in diverse signaling pathways","volume":"109","author":"Guo","year":"2012","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"136","DOI":"10.1002\/bip.22126","article-title":"The many facets of MLL1 regulation","volume":"99","author":"Zhang","year":"2013","journal-title":"Biopolymers"},{"key":"ref_31","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_32","doi-asserted-by":"crossref","first-page":"1391","DOI":"10.1002\/cmdc.202000972","article-title":"A box of chemistry to inhibit the MEN1 tumor suppressor gene promoting leukemia","volume":"16","author":"Nizamuddin","year":"2021","journal-title":"ChemMedChem"},{"key":"ref_33","first-page":"1729","article-title":"Downregulation of RUNX1\/CBF\u03b2 by MLL fusion proteins enhances hematopoietic stem cell self-renewal","volume":"123","author":"Zhao","year":"2014","journal-title":"Blood J. Am. Soc. Hematol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1793","DOI":"10.1038\/leu.2013.200","article-title":"RUNX1 meets MLL: Epigenetic regulation of hematopoiesis by two leukemia genes","volume":"27","author":"Koh","year":"2013","journal-title":"Leukemia"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1106","DOI":"10.1016\/j.cell.2008.04.043","article-title":"Integration of external signaling pathways with the core transcriptional network in embryonic stem cells","volume":"133","author":"Chen","year":"2008","journal-title":"Cell"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"15278","DOI":"10.1038\/ncomms15278","article-title":"Menin enhances c-Myc-mediated transcription to promote cancer progression","volume":"8","author":"Wu","year":"2017","journal-title":"Nat. Commun."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"10770","DOI":"10.1073\/pnas.1834524100","article-title":"Transcription factor JunD, deprived of menin, switches from growth suppressor to growth promoter","volume":"100","author":"Agarwal","year":"2003","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"4706","DOI":"10.1038\/sj.onc.1203832","article-title":"Identification and characterization of JunD missense mutants that lack menin binding","volume":"19","author":"Knapp","year":"2000","journal-title":"Oncogene"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"6434","DOI":"10.1038\/sj.onc.1205822","article-title":"Menin uncouples Elk-1, JunD and c-Jun phosphorylation from MAP kinase activation","volume":"21","author":"Gallo","year":"2002","journal-title":"Oncogene"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"49045","DOI":"10.1074\/jbc.M409358200","article-title":"Direct binding of DNA by tumor suppressor menin","volume":"279","author":"La","year":"2004","journal-title":"J. Biol. Chem."},{"key":"ref_41","first-page":"4204","article-title":"Menin associates with FANCD2, a protein involved in repair of DNA damage","volume":"63","author":"Jin","year":"2003","journal-title":"Cancer Res."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"441","DOI":"10.1182\/blood-2005-07-3011","article-title":"Analysis of prognostic factors of acute lymphoblastic leukemia in infants: Report on CCG 1953 from the Children\u2019s Oncology Group","volume":"108","author":"Hilden","year":"2006","journal-title":"Blood"},{"key":"ref_43","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_44","doi-asserted-by":"crossref","first-page":"521","DOI":"10.1038\/sj.leu.2403253","article-title":"In vitro drug-resistance profile in infant acute lymphoblastic leukemia in relation to age, MLL rearrangements and immunophenotype","volume":"18","author":"Beverloo","year":"2004","journal-title":"Leukemia"},{"key":"ref_45","first-page":"205","article-title":"How I treat infant leukemia","volume":"133","author":"Brown","year":"2019","journal-title":"Blood J. Am. Soc. Hematol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"459","DOI":"10.1002\/cncr.30376","article-title":"Prognostic impact of pretreatment cytogenetics in adult P hiladelphia chromosome\u2013negative acute lymphoblastic leukemia in the era of minimal residual disease","volume":"123","author":"Issa","year":"2017","journal-title":"Cancer"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"836","DOI":"10.1038\/leu.2012.319","article-title":"Prognostic significance of 11q23 aberrations in adult acute myeloid leukemia and the role of allogeneic stem cell transplantation","volume":"27","author":"Chen","year":"2013","journal-title":"Leukemia"},{"key":"ref_48","first-page":"2039","article-title":"Distinct pathways regulated by menin and by MLL1 in hematopoietic stem cells and developing B cells","volume":"122","author":"Li","year":"2013","journal-title":"Blood J. Am. Soc. Hematol."},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"Wang, R., Xu, P., Chang, L.-L., Zhang, S.-Z., and Zhu, H.-H. (2022). Targeted therapy in NPM1-mutated AML: Knowns and unknowns. Front. Oncol., 12.","DOI":"10.3389\/fonc.2022.972606"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"1931","DOI":"10.1182\/blood.2023023096","article-title":"Postinduction molecular MRD identifies patients with NPM1 AML who benefit from allogeneic transplant in first remission","volume":"143","author":"Othman","year":"2024","journal-title":"Blood"},{"key":"ref_51","first-page":"2776","article-title":"The impact of FLT3 internal tandem duplication mutant level, number, size, and interaction with NPM1 mutations in a large cohort of young adult patients with acute myeloid leukemia","volume":"111","author":"Gale","year":"2008","journal-title":"Blood J. Am. Soc. Hematol."},{"key":"ref_52","first-page":"2281","article-title":"Terminal deoxynucleotidyl transferase promotes acute myeloid leukemia by priming FLT3-ITD replication slippage","volume":"134","author":"Borrow","year":"2019","journal-title":"Blood J. Am. Soc. Hematol."},{"key":"ref_53","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_54","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_55","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_56","doi-asserted-by":"crossref","first-page":"244","DOI":"10.3390\/hematolrep16020024","article-title":"A 2024 Update on Menin Inhibitors. A New Class of Target Agents against KMT2A-Rearranged and NPM1-Mutated Acute Myeloid Leukemia","volume":"16","author":"Candoni","year":"2024","journal-title":"Hematol. Rep."},{"key":"ref_57","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_58","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_59","doi-asserted-by":"crossref","first-page":"180","DOI":"10.1016\/j.ccr.2012.06.032","article-title":"ASXL1 mutations promote myeloid transformation through loss of PRC2-mediated gene repression","volume":"22","author":"Adli","year":"2012","journal-title":"Cancer Cell"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"1654","DOI":"10.1016\/j.celrep.2017.05.005","article-title":"RUNX1-ETO and RUNX1-EVI1 Differentially Reprogram the Chromatin Landscape in t (8; 21) and t (3; 21) AML","volume":"19","author":"Loke","year":"2017","journal-title":"Cell Rep."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"711","DOI":"10.2147\/OTT.S95279","article-title":"Higher expression levels of the HOXA9 gene, closely associated with MLL-PTD and EZH2 mutations, predict inferior outcome in acute myeloid leukemia","volume":"9","author":"Gao","year":"2016","journal-title":"OncoTargets Ther."},{"key":"ref_62","first-page":"4668","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 J. Am. Soc. Hematol."},{"key":"ref_63","first-page":"894","article-title":"The menin-MLL1 interaction is a molecular dependency in NUP98-rearranged AML","volume":"139","author":"Heikamp","year":"2022","journal-title":"Blood J. Am. Soc. Hematol."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"620","DOI":"10.1016\/j.semcdb.2009.03.003","article-title":"Nuclear pore proteins and cancer","volume":"20","author":"Xu","year":"2009","journal-title":"Semin. Cell Dev. Biol."},{"key":"ref_65","first-page":"2275","article-title":"Mechanistic insights and potential therapeutic approaches for NUP98-rearranged hematologic malignancies","volume":"136","author":"Michmerhuizen","year":"2020","journal-title":"Blood J. Am. Soc. Hematol."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"2298","DOI":"10.1101\/gad.1111603","article-title":"Transformation of myeloid progenitors by MLL oncoproteins is dependent on Hoxa7 and Hoxa9","volume":"17","author":"Ayton","year":"2003","journal-title":"Genes Dev."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"1948","DOI":"10.1038\/sj.leu.2403891","article-title":"CALM-AF10+ T-ALL expression profiles are characterized by overexpression of HOXA and BMI1 oncogenes","volume":"19","author":"Dik","year":"2005","journal-title":"Leukemia"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"3747","DOI":"10.1182\/blood-2005-05-2168","article-title":"Mutations in nucleophosmin (NPM1) in acute myeloid leukemia (AML): Association with other gene abnormalities and previously established gene expression signatures and their favorable prognostic significance","volume":"106","author":"Verhaak","year":"2005","journal-title":"Blood"},{"key":"ref_69","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_70","doi-asserted-by":"crossref","first-page":"596","DOI":"10.1200\/JCO.2009.25.1496","article-title":"Favorable prognostic impact of NPM1 mutations in older patients with cytogenetically normal de novo acute myeloid leukemia and associated gene-and microRNA-expression signatures: A Cancer and Leukemia Group B study","volume":"28","author":"Becker","year":"2010","journal-title":"J. Clin. Oncol."},{"key":"ref_71","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_72","first-page":"1558","article-title":"Global down-regulation of HOX gene expression in PML-RAR\u03b1+ acute promyelocytic leukemia identified by small-array real-time PCR","volume":"101","author":"Thompson","year":"2003","journal-title":"Blood J. Am. Soc. Hematol."},{"key":"ref_73","first-page":"2332","article-title":"NUP98-MLL fusion in human acute myeloblastic leukemia","volume":"116","author":"Kaltenbach","year":"2010","journal-title":"Blood J. Am. Soc. Hematol."},{"key":"ref_74","first-page":"5371","article-title":"High BAALC expression associates with other molecular prognostic markers, poor outcome, and a distinct gene-expression signature in cytogenetically normal patients younger than 60 years with acute myeloid leukemia: A Cancer and Leukemia Group B (CALGB) study","volume":"111","author":"Langer","year":"2008","journal-title":"Blood J. Am. Soc. Hematol."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"5078","DOI":"10.1200\/JCO.2008.17.5554","article-title":"Prognostic significance of, and gene and microRNA expression signatures associated with, CEBPA mutations in cytogenetically normal acute myeloid leukemia with high-risk molecular features: A Cancer and Leukemia Group B Study","volume":"26","author":"Marcucci","year":"2008","journal-title":"J. Clin. Oncol."},{"key":"ref_76","doi-asserted-by":"crossref","unstructured":"Issa, G.C., Aldoss, I., Thirman, M.J., DiPersio, J., Arellano, M., Blachly, J.S., Mannis, G.N., Perl, A., Dickens, D.S., and McMahon, C.M. (2024). Menin Inhibition with Revumenib for KMT2A-Rearranged Relapsed or Refractory Acute Leukemia (AUGMENT-101). J. Clin. Oncol., 20.","DOI":"10.1200\/JCO.24.00826"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1182\/blood-2023-172422","article-title":"A first-in-human phase 1 study of the menin-KMT2A (MLL1) inhibitor JNJ-75276617 in adult patients with relapsed\/refractory acute leukemia harboring KMT2A or NPM1 alterations","volume":"142","author":"Jabbour","year":"2023","journal-title":"Blood"},{"key":"ref_78","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_79","doi-asserted-by":"crossref","first-page":"166","DOI":"10.1182\/blood-2023-185561","article-title":"Combining menin and MEK inhibition to target poor prognostic KMT2A-rearranged RAS pathway-mutant acute leukemia","volume":"142","author":"Scheidegger","year":"2023","journal-title":"Blood"},{"key":"ref_80","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_81","doi-asserted-by":"crossref","first-page":"4168","DOI":"10.1182\/blood-2023-190638","article-title":"The clinical menin inhibitor ziftomenib and the nuclear export inhibitor selinexor synergistically inhibit the growth of MLL-r AML","volume":"142","author":"Uddin","year":"2023","journal-title":"Blood"},{"key":"ref_82","first-page":"2442","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 J. Am. Soc. Hematol."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1182\/blood-2023-182337","article-title":"Early results of the phase I\/II study investigating the all-oral combination of the menin inhibitor revumenib (SNDX-5613) with decitabine\/cedazuridine (ASTX727) and venetoclax in acute myeloid leukemia (SAVE)","volume":"142","author":"Issa","year":"2023","journal-title":"Blood"},{"key":"ref_84","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_85","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_86","first-page":"64","article-title":"The future of HOXA-expressing leukemias: Menin inhibitor response and resistance","volume":"31","author":"Wenge","year":"2024","journal-title":"Curr. Opin. Hematol."},{"key":"ref_87","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_88","doi-asserted-by":"crossref","first-page":"384","DOI":"10.1038\/s41392-023-01627-w","article-title":"Targeting menin: A promising therapeutic strategy for susceptible acute leukemia subtypes","volume":"8","year":"2023","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"735","DOI":"10.1002\/ajh.26142","article-title":"Differentiation syndrome with lower-intensity treatments for acute myeloid leukemia","volume":"96","author":"Fathi","year":"2021","journal-title":"Am. J. Hematol."},{"key":"ref_90","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_91","doi-asserted-by":"crossref","first-page":"699","DOI":"10.1182\/blood-2021-146944","article-title":"Safety and efficacy of menin inhibition in patients (Pts) with MLL-rearranged and NPM1 mutant acute leukemia: A phase (Ph) 1, first-in-human study of SNDX-5613 (AUGMENT 101)","volume":"138","author":"Stein","year":"2021","journal-title":"Blood"},{"key":"ref_92","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_93","first-page":"2777","article-title":"How we prevent and treat differentiation syndrome in patients with acute promyelocytic leukemia","volume":"123","author":"Sanz","year":"2014","journal-title":"Blood J. Am. Soc. Hematol."},{"key":"ref_94","doi-asserted-by":"crossref","unstructured":"Wolffhardt, T.M., Ketzer, F., Telese, S., Wirth, T., and Ushmorov, A. (2023). Dependency of B-Cell Acute Lymphoblastic Leukemia and Multiple Myeloma Cell Lines on MEN1 Extends beyond MEN1\u2013KMT2A Interaction. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms242216472"}],"container-title":["Cancers"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6694\/16\/22\/3743\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T16:27:06Z","timestamp":1760113626000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6694\/16\/22\/3743"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,11,6]]},"references-count":94,"journal-issue":{"issue":"22","published-online":{"date-parts":[[2024,11]]}},"alternative-id":["cancers16223743"],"URL":"https:\/\/doi.org\/10.3390\/cancers16223743","relation":{},"ISSN":["2072-6694"],"issn-type":[{"value":"2072-6694","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,11,6]]}}}