{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T03:20:23Z","timestamp":1790911223461,"version":"4.1.0"},"reference-count":101,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2025,1,4]],"date-time":"2025-01-04T00:00:00Z","timestamp":1735948800000},"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>Menin (MEN1) is a well-recognized powerful tumor promoter in acute leukemias (AL) with KMT2A rearrangements (KMT2Ar, also known as MLL) and mutant nucleophosmin 1 (NPM1m) acute myeloid leukemia (AML). MEN1 is essential for sustaining leukemic transformation due to its interaction with wild-type KMT2A and KMT2A fusion proteins, leading to the dysregulation of KMT2A target genes. MEN1 inhibitors (MIs), such as revumenib, ziftomenib, and other active small molecules, represent a promising new class of therapies currently under clinical development. By disrupting the MEN1-KMT2Ar complex, a group of proteins involved in chromatin remodeling, MIs induce apoptosis and differentiation AL expressing KMT2Ar or NPM1m AML. Phase I and II clinical trials have evaluated MIs as standalone treatments and combined them with other synergistic drugs, yielding promising results. These trials have demonstrated notable response rates with manageable toxicities. Among MIs, ziftomenib received orphan drug and breakthrough therapy designations from the European Medicines Agency in January 2024 and the Food and Drug Administration (FDA) in April 2024, respectively, for treating R\/R patients with NPM1m AML. Additionally, in November 2024, the FDA approved revumenib for treating R\/R patients with KMT2Ar-AL. This review focuses on the pathophysiology of MI-sensitive AL, primarily AML. It illustrates data from clinical trials and discusses the emergence of resistance mechanisms. In addition, we outline future directions for the use of MIs and emphasize the need for further research to fully realize the potential of these novel compounds, especially in the context of specific genetic subtypes of challenging AL.<\/jats:p>","DOI":"10.3390\/cancers17010142","type":"journal-article","created":{"date-parts":[[2025,1,6]],"date-time":"2025-01-06T04:37:10Z","timestamp":1736138230000},"page":"142","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Menin Inhibitors: New Targeted Therapies for Specific Genetic Subtypes of Difficult-to-Treat Acute Leukemias"],"prefix":"10.3390","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2226-6518","authenticated-orcid":false,"given":"Pasquale","family":"Niscola","sequence":"first","affiliation":[{"name":"Hematology Unit, S. Eugenio Hospital (ASL Roma 2), 00122 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valentina","family":"Gianfelici","sequence":"additional","affiliation":[{"name":"Hematology Unit, S. Eugenio Hospital (ASL Roma 2), 00122 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marco","family":"Giovannini","sequence":"additional","affiliation":[{"name":"Hematology Unit, S. Eugenio Hospital (ASL Roma 2), 00122 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniela","family":"Piccioni","sequence":"additional","affiliation":[{"name":"Hematology Unit, S. Eugenio Hospital (ASL Roma 2), 00122 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carla","family":"Mazzone","sequence":"additional","affiliation":[{"name":"Hematology Unit, S. Eugenio Hospital (ASL Roma 2), 00122 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paolo de","family":"Fabritiis","sequence":"additional","affiliation":[{"name":"Hematology Unit, S. Eugenio Hospital (ASL Roma 2), 00122 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,1,4]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Majer, A.D., Hua, X., and Katona, B.W. (2024). Menin in Cancer. Genes, 15.","DOI":"10.3390\/genes15091231"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"812","DOI":"10.1111\/bjh.19508","article-title":"The Menin story in acute myeloid leukaemia-The road to success","volume":"205","author":"Ganser","year":"2024","journal-title":"Br. J. Haematol."},{"key":"ref_3","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_4","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1182\/hematology.2022000325","article-title":"Novel investigational approaches for high-risk genetic subsets of AML: TP53, KMT2A, FLT3","volume":"2022","author":"Sahasrabudhe","year":"2022","journal-title":"Hematology"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"szae089","DOI":"10.1093\/stcltm\/szae089","article-title":"Targeting chromatin modifying complexes in acute myeloid leukemia","volume":"28","author":"Schurer","year":"2024","journal-title":"Stem Cells Transl. Med."},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Guarnera, L., D\u2019Addona, M., Bravo-Perez, C., and Visconte, V. (2024). KMT2A Rearrangements in Leukemias: Molecular Aspects and Therapeutic Perspectives. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms25169023"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1186\/s13045-021-01057-7","article-title":"Structure, function and inhibition of critical protein-protein interactions involving mixed lineage leukemia one and its fusion oncoproteins","volume":"14","author":"Li","year":"2021","journal-title":"J. Hematol. Oncol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"229","DOI":"10.1159\/000536152","article-title":"Pathophysiology of Acute Myeloid Leukemia","volume":"147","author":"Wachter","year":"2024","journal-title":"Acta Haematol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"556","DOI":"10.1007\/s12185-024-03835-8","article-title":"Recent advances in AML with mutated NPM1","volume":"120","author":"Ishikawa","year":"2024","journal-title":"Int. J. Hematol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1159\/000530253","article-title":"NPM1-Mutated Acute Myeloid Leukemia: Recent Developments and Open Questions","volume":"91","author":"Patel","year":"2024","journal-title":"Pathobiology"},{"key":"ref_11","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_12","doi-asserted-by":"crossref","unstructured":"Sharma, N., and Liesveld, J.L. (2023). NPM 1 Mutations in AML\u2014The Landscape in 2023. Cancers, 15.","DOI":"10.3390\/cancers15041177"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"550","DOI":"10.1002\/ajh.26862","article-title":"Mutant NPM1: Nuclear export and the mechanism of leukemogenesis","volume":"98","author":"Falini","year":"2023","journal-title":"Am. J. Hematol."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Taha, M.S., and Ahmadian, M.R. (2024). Nucleophosmin: A Nucleolar Phosphoprotein Orchestrating Cellular Stress Responses. Cells, 13.","DOI":"10.3390\/cells13151266"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1707","DOI":"10.1182\/blood.2019004226","article-title":"NPM1-mutated acute myeloid leukemia: From bench to bedside","volume":"136","author":"Falini","year":"2020","journal-title":"Blood"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"988","DOI":"10.1038\/s41375-023-01877-1","article-title":"The KMT2A recombinome of acute leukemias in 2023","volume":"37","author":"Meyer","year":"2023","journal-title":"Leukemia"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1856","DOI":"10.1002\/cncr.34728","article-title":"Early mortality in acute myeloid leukemia with KMT2A rearrangement is associated with high risk of bleeding and disseminated intravascular coagulation","volume":"129","author":"Nguyen","year":"2023","journal-title":"Cancer"},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Adriaanse, F.R.S., Schneider, P., Arentsen-Peters, S.T.C.J.M., Fonseca, A.M.N.D., Stutterheim, J., Pieters, R., Zwaan, C.M., and Stam, R.W. (2024). Distinct Responses to Menin Inhibition and Synergy with DOT1L Inhibition in KMT2A-Rearranged Acute Lymphoblastic and Myeloid Leukemia. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms25116020"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"e70126","DOI":"10.1111\/jcmm.70126","article-title":"Molecular characterization and biomarker identification in paediatric B-cell acute lymphoblastic leukaemia","volume":"28","author":"Du","year":"2024","journal-title":"J. Cell Mol. Med."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"102191","DOI":"10.1016\/j.gde.2024.102191","article-title":"Chromatin and aberrant enhancer activity in KMT2A rearranged acute lymphoblastic leukemia","volume":"86","author":"Milne","year":"2024","journal-title":"Curr. Opin. Genet. Dev."},{"key":"ref_21","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_22","doi-asserted-by":"crossref","first-page":"1245","DOI":"10.1038\/s41375-023-01906-z","article-title":"UBTF tandem duplications define a distinct subtype of adult de novo acute myeloid leukemia","volume":"37","author":"Duployez","year":"2023","journal-title":"Leukemia"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"2323","DOI":"10.1056\/NEJMc2404110","article-title":"Response and Resistance to Menin Inhibitor in UBTF-Tandem Duplication AML","volume":"390","author":"Tiong","year":"2024","journal-title":"N. Engl. J. Med."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"894","DOI":"10.1182\/blood.2021012806","article-title":"The main-MLL1 interaction is a molecular dependency in NUP98-rearranged AML","volume":"139","author":"Heikamp","year":"2022","journal-title":"Blood"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1907","DOI":"10.1080\/10428194.2022.2047672","article-title":"Adult acute myeloid leukemia patients with NUP98 rearrangement have frequent cryptic translocations and unfavorable outcome","volume":"63","author":"Xie","year":"2022","journal-title":"Leuk Lymphoma"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"53","DOI":"10.3343\/alm.2024.0190","article-title":"Rare Non-Cryptic NUP98 Rearrangements Associated With Myeloid Neoplasms and Their Poor Prognostic Impact","volume":"45","author":"Park","year":"2024","journal-title":"Ann. Lab. Med"},{"key":"ref_27","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_28","doi-asserted-by":"crossref","first-page":"e70013","DOI":"10.1002\/hem3.70013","article-title":"NUP98 oncofusions in myeloid malignancies: An update on molecular mechanisms and therapeutic opportunities","volume":"8","author":"Rasouli","year":"2024","journal-title":"Hemasphere"},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"George, B.S., Yohannan, B., Gonzalez, A., and Rios, A. (2022). Mixed-Phenotype Acute Leukemia: Clinical Diagnosis and Therapeutic Strategies. Biomedicines, 10.","DOI":"10.3390\/biomedicines10081974"},{"key":"ref_30","first-page":"1","article-title":"NPM1-fusion proteins promote myeloid leukemogenesis through XPO1-dependent HOX activation","volume":"23","author":"Shimosato","year":"2024","journal-title":"Leukemia"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1417","DOI":"10.1001\/jamaoncol.2024.2662","article-title":"Contemporary Management of Acute Myeloid Leukemia: A Review","volume":"8","author":"Venugopal","year":"2024","journal-title":"JAMA Oncol."},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Diekmann, B., Veeger, N., Rozema, J., Kibbelaar, R., Franken, B., G\u00fcler, Y., Adema, B., van Roon, E., and Hoogendoorn, M. (2024). The Evolution of Treatment Policies and Outcomes for Patients Aged 60 and Older with Acute Myeloid Leukemia: A Population-Based Analysis over Two Decades. Cancers, 16.","DOI":"10.3390\/cancers16233907"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"6632","DOI":"10.3390\/curroncol31110490","article-title":"Acute Myeloid Leukemia in Older Patients: From New Biological Insights to Targeted Therapies","volume":"31","author":"Niscola","year":"2024","journal-title":"Curr. Oncol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1007\/s40487-024-00262-x","article-title":"Small Molecule Menin Inhibitors: Novel Therapeutic Agents Targeting Acute Myeloid Leukemia with KMT2A Rearrangement or NPM1 Mutation","volume":"12","author":"Thomas","year":"2024","journal-title":"Oncol. Ther."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1703","DOI":"10.1038\/s41375-022-01613-1","article-title":"The 5th edition of the World Health Organization Classification of Haematolymphoid Tumours: Myeloid and Histiocytic\/Dendritic Neoplasms","volume":"36","author":"Khoury","year":"2022","journal-title":"Leukemia"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1200","DOI":"10.1182\/blood.2022015850","article-title":"International Consensus Classification of Myeloid Neoplasms and Acute Leukemias: Integrating morphologic, clinical, and genomic data","volume":"140","author":"Arber","year":"2022","journal-title":"Blood"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1345","DOI":"10.1182\/blood.2022016867","article-title":"Diagnosis and management of AML in adults: 2022 recommendations from an international expert panel on behalf of the ELN","volume":"140","author":"Wei","year":"2022","journal-title":"Blood"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"569","DOI":"10.1097\/CCO.0000000000001094","article-title":"Advances in the pathogenesis of FLT3 -mutated acute myeloid leukemia and targeted treatments","volume":"36","author":"Travaglini","year":"2024","journal-title":"Curr. Opin. Oncol."},{"key":"ref_39","first-page":"708","article-title":"How I Treat: Differentiation Therapy in Acute Myeloid Leukemia","volume":"144","author":"Issa","year":"2024","journal-title":"Blood"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"755","DOI":"10.1080\/17474086.2024.2422554","article-title":"A review of the isocitrate dehydrogenase inhibitors in management of adult patients with AML and MDS","volume":"17","author":"Norman","year":"2024","journal-title":"Expert Rev. Hematol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"2267","DOI":"10.2147\/CMAR.S195723","article-title":"Profile of Glasdegib for the Treatment of Newly Diagnosed Acute Myeloid Leukemia (AML): Evidence to Date","volume":"14","author":"Iyer","year":"2022","journal-title":"Cancer Manag. Res."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"615","DOI":"10.1002\/ajh.27246","article-title":"Long-term follow-up of VIALE-A: Venetoclax and azacitidine in chemotherapy-ineligible untreated acute myeloid leukemia","volume":"99","author":"Pratz","year":"2024","journal-title":"Am. J. Hematol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"e835","DOI":"10.1016\/j.clml.2024.07.004","article-title":"Safety, Efficacy, and Predictive Factors of Venetoclax-Based Regimens in Elderly Acute Myeloid Leukemia Patients: A Meta-Analysis","volume":"24","author":"Qureshi","year":"2024","journal-title":"Clin. Lymphoma Myeloma Leuk."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"blood-2024024011","DOI":"10.1182\/blood.2024024011","article-title":"How I Treat: Secondary Acute Myeloid Leukemia","volume":"2","author":"Green","year":"2024","journal-title":"Blood"},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Auerbach, S., Puka, B., Golla, U., and Chachoua, I. (2024). Recent Advances towards the Understanding of Secondary Acute Myeloid Leukemia Progression. Life, 14.","DOI":"10.20944\/preprints202401.1918.v1"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"e70326","DOI":"10.1002\/cam4.70326","article-title":"Recent Developments and Evolving Therapeutic Strategies in KMT2A-Rearranged Acute Leukemia","volume":"13","author":"Yin","year":"2024","journal-title":"Cancer Med."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"536","DOI":"10.1158\/2159-8290.CD-19-0710","article-title":"Monocytic Subclones Confer Resistance to Venetoclax-Based Therapy in Patients with Acute Myeloid Leukemia","volume":"10","author":"Pei","year":"2020","journal-title":"Cancer Discov."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"160","DOI":"10.1159\/000534897","article-title":"Non-Immunotherapy Approaches for Relapsed or Refractory AML: An Update for 2024","volume":"147","author":"Buchrits","year":"2024","journal-title":"Acta Haematol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"439","DOI":"10.1007\/s12185-024-03827-8","article-title":"Precision medicine in AML: Overcoming resistance","volume":"120","author":"Urrutia","year":"2024","journal-title":"Int. J. Hematol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"723","DOI":"10.1080\/17474086.2024.2402283","article-title":"Relapse and resistance in acute myeloid leukemia post venetoclax: Improving second lines therapy and combinations","volume":"17","author":"Shahswar","year":"2024","journal-title":"Expert Rev. Hematol."},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"Premnath, N., and Madanat, Y.F. (2023). Novel Investigational Agents and Pathways That May Influence the Future Management of Acute Myeloid Leukemia. Cancers, 15.","DOI":"10.3390\/cancers15112958"},{"key":"ref_52","doi-asserted-by":"crossref","unstructured":"Shukla, M., Abdul-Hay, M., and Choi, J.H. (2024). Molecular Features and Treatment Paradigms of Acute Myeloid Leukemia. Biomedicines, 12.","DOI":"10.3390\/biomedicines12081768"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1038\/s41408-024-01143-2","article-title":"Current status and research directions in acute myeloid leukemia","volume":"14","author":"Kantarjian","year":"2024","journal-title":"Blood Cancer J."},{"key":"ref_54","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_55","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_56","doi-asserted-by":"crossref","first-page":"9451","DOI":"10.1007\/s00432-023-04752-9","article-title":"Targeting the undruggable: Menin inhibitors ante portas","volume":"149","author":"Dempke","year":"2023","journal-title":"J. Cancer Res. Clin. Oncol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1186\/s13045-024-01632-8","article-title":"Menin inhibitors for the treatment of acute myeloid leukemia: Challenges and opportunities ahead","volume":"17","author":"Nadiminti","year":"2024","journal-title":"J. Hematol. Oncol."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"e77","DOI":"10.1002\/hem3.77","article-title":"Induction of AML cell differentiation using HOXA9\/DNA binding inhibitors as a potential therapeutic option for HOXA9-dependent AML","volume":"8","author":"Lambert","year":"2024","journal-title":"Hemasphere"},{"key":"ref_59","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_60","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_61","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_62","doi-asserted-by":"crossref","first-page":"2768","DOI":"10.1182\/blood-2024-206075","article-title":"Combined Use of Ziftomenib and Selinexor Is Effective in NPM1 Mutant Acute Myeloid Leukemia","volume":"144","author":"Dhiman","year":"2024","journal-title":"Blood"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"5938","DOI":"10.1182\/bloodadvances.2022007563","article-title":"Prolonged XPO1 inhibition is essential for optimal antileukemic activity in NPM1-mutated AML","volume":"6","author":"Pianigiani","year":"2022","journal-title":"Blood Adv."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1038\/s41392-021-00762-6","article-title":"Wnt\/\u03b2-catenin signalling: Function, biological mechanisms, and therapeutic opportunities","volume":"7","author":"Liu","year":"2022","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_65","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_66","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_67","doi-asserted-by":"crossref","unstructured":"Arthur, M.N., Bebla, K., Broni, E., Ashley, C., Velazquez, M., Hua, X., Radhakrishnan, R., Kwofie, S.K., and Miller, W.A. (2024). Design of Inhibitors That Target the Menin-Mixed-Lineage Leukemia Interaction. Computation, 12.","DOI":"10.3390\/computation12010003"},{"key":"ref_68","first-page":"185","article-title":"The development of menin inhibitors in AML and ALL","volume":"22","author":"Issa","year":"2024","journal-title":"Clin. Adv. Hematol. Oncol."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1186\/s13045-024-01573-2","article-title":"Menin inhibitors for acute myeloid leukemia: Latest updates from the 2023 ASH Annual Meeting","volume":"17","author":"An","year":"2024","journal-title":"J. Hematol. Oncol."},{"key":"ref_70","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_71","doi-asserted-by":"crossref","first-page":"192","DOI":"10.1182\/hematology.2023000429","article-title":"The future paradigm of HMA + VEN or targeted inhibitor approaches: Sequencing or triplet combinations in AML therapy","volume":"2023","author":"Venugopal","year":"2023","journal-title":"Hematol. Am. Soc. Hematol. Educ. Program"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1111\/bjh.19519","article-title":"Combination therapy with novel agents for acute myeloid leukaemia: Insights into treatment of a heterogenous disease","volume":"205","author":"Jen","year":"2024","journal-title":"Br. J. Haematol."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"2729","DOI":"10.1038\/s41375-022-01707-w","article-title":"The activity of menin inhibitor ziftomenib (KO-539) as monotherapy or in combinations against AML cells with MLL1 rearrangement or mutant NPM1","volume":"36","author":"Fiskus","year":"2022","journal-title":"Leukemia"},{"key":"ref_74","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_75","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_76","doi-asserted-by":"crossref","first-page":"2880","DOI":"10.1182\/blood-2024-199170","article-title":"Ziftomenib Combined with Venetoclax\/Azacitidine in Relapsed\/Refractory NPM1-m or KMT2A-r Acute Myeloid Leukemia: Interim Phase 1a Results from KOMET-007","volume":"142","author":"Fathi","year":"2024","journal-title":"Blood"},{"key":"ref_77","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_78","doi-asserted-by":"crossref","first-page":"214","DOI":"10.1182\/blood-2024-198218","article-title":"Ziftomenib Combined with Intensive Induction (7 + 3) in Newly Diagnosed NPM1-m or KMT2A-r Acute Myeloid Leukemia: Interim Phase 1a Results from KOMET-007","volume":"142","author":"Zeidan","year":"2024","journal-title":"Blood"},{"key":"ref_79","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_80","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_81","doi-asserted-by":"crossref","unstructured":"Ray, J., Clegg, B., Grembecka, J., and Cierpicki, T. (2024). Drug-resistant menin variants retain high binding affinity and interactions with MLL1. J. Biol. Chem., 300.","DOI":"10.1016\/j.jbc.2024.107777"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"1139","DOI":"10.1182\/blood.2024025760","article-title":"A menin-KMT2A inhibitor to overcome resistance","volume":"144","author":"Heckman","year":"2024","journal-title":"Blood"},{"key":"ref_83","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_84","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_85","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_86","doi-asserted-by":"crossref","unstructured":"Carraway, H.E., Nakitandwe, J., Cacovean, A., Ma, Y., Munneke, B., Waghmare, G., Mandap, C., Ahmed, U., Kowalczyk, N., and Butler, T. (2024). Complete remission of NUP98 fusion-positive acute myeloid leukemia with the covalent menin inhibitor BMF-219, icovamenib. Haematologica.","DOI":"10.3324\/haematol.2024.286537"},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"3586","DOI":"10.1182\/blood-2024-202042","article-title":"Discovery of BTC-86, a Novel Second-Generation Menin-MLL Inhibitor to Overcome the Acquired Resistance in MEN1 for R\/R Acute Leukemia","volume":"144","author":"Liu","year":"2024","journal-title":"Blood"},{"key":"ref_88","first-page":"JCO2400826","article-title":"Menin Inhibition with Revumenib for KMT2A-Rearranged Relapsed or Refractory Acute Leukemia (AUGMENT-101)","volume":"9","author":"Issa","year":"2024","journal-title":"J. Clin. Oncol."},{"key":"ref_89","first-page":"JCO2401265","article-title":"Revumenib Revises the Treatment Landscape for KMT2A-r Leukemia","volume":"7","author":"Heikamp","year":"2024","journal-title":"J. Clin. Oncol."},{"key":"ref_90","first-page":"3488","article-title":"Revumenib for patients with acute leukemia: A new tool for differentiation therapy","volume":"109","author":"Salman","year":"2024","journal-title":"Haematologica"},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1182\/blood-2022-167412","article-title":"Update on a Phase 1\/2 First-in-Human Study of the Menin-KMT2A (MLL) Inhibitor Ziftomenib (KO-539) in Patients with Relapsed or Refractory Acute Myeloid Leukemia","volume":"140","author":"Erba","year":"2022","journal-title":"Blood"},{"key":"ref_92","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_93","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_94","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_95","doi-asserted-by":"crossref","first-page":"1452","DOI":"10.1002\/ajh.26989","article-title":"NPM1-mutated acute myeloid leukemia: New pathogenetic and therapeutic insights and open questions","volume":"98","author":"Falini","year":"2023","journal-title":"Am. J. Hematol."},{"key":"ref_96","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_97","doi-asserted-by":"crossref","first-page":"213","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_98","doi-asserted-by":"crossref","unstructured":"Fedorov, K., Maiti, A., and Konopleva, M. (2023). Targeting FLT3 Mutation in Acute Myeloid Leukemia: Current Strategies and Future Directions. Cancers, 15.","DOI":"10.3390\/cancers15082312"},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1182\/hematology.2020000089","article-title":"Management of toxicities associated with targeted therapies for acute myeloid leukemia: When to push through and when to stop. Hematol","volume":"2020","author":"Wang","year":"2020","journal-title":"Am. Soc. Hematol. Educ. Program"},{"key":"ref_100","doi-asserted-by":"crossref","unstructured":"Potenza, L., Borelli, E., Bigi, S., Giusti, D., Longo, G., Odejide, O., Porro, C.A., Zimmermann, C., Efficace, F., and Bruera, E. (2022). Early Palliative Care in Acute Myeloid Leukemia. Cancers, 14.","DOI":"10.3390\/cancers14030478"},{"key":"ref_101","doi-asserted-by":"crossref","unstructured":"Kantarjian, H.M., DiNardo, C.D., Kadia, T.M., Daver, N.G., Altman, J.K., Stein, E.M., Jabbour, E., Schiffer, C.A., Lang, A., and Ravandi, F. (2024). Acute myeloid leukemia management and research in 2025. CA Cancer J. Clin., 10.","DOI":"10.3322\/caac.21873"}],"container-title":["Cancers"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6694\/17\/1\/142\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,8]],"date-time":"2025-10-08T10:23:01Z","timestamp":1759918981000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6694\/17\/1\/142"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,1,4]]},"references-count":101,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2025,1]]}},"alternative-id":["cancers17010142"],"URL":"https:\/\/doi.org\/10.3390\/cancers17010142","relation":{},"ISSN":["2072-6694"],"issn-type":[{"value":"2072-6694","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,1,4]]}}}