{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Bourgeois W"],"funding":["NHLBI NIH HHS","European Hematology Association","NCI NIH HHS"],"pagination":["1513-1527"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC11033588"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["143(15)"],"pubmed_abstract":["<h4>Abstract</h4>Small molecules that target the menin-KMT2A protein-protein interaction (menin inhibitors) have recently entered clinical trials in lysine methyltransferase 2A (KMT2A or MLL1)-rearranged (KMT2A-r) and nucleophosmin-mutant (NPM1c) acute myeloid leukemia (AML) and are demonstrating encouraging results. However, rationally chosen combination therapy is needed to improve responses and prevent resistance. We have previously identified IKZF1/IKAROS as a target in KMT2A-r AML and shown in preclinical models that IKAROS protein degradation with lenalidomide or iberdomide has modest single-agent activity yet can synergize with menin inhibitors. Recently, the novel IKAROS degrader mezigdomide was developed with greatly enhanced IKAROS protein degradation. In this study, we show that"],"journal":["Blood"],"pubmed_title":["Mezigdomide is effective alone and in combination with menin inhibition in preclinical models of KMT2A-r and NPM1c AML."],"pmcid":["PMC11033588"],"funding_grant_id":["K99 CA279888","P50 CA206963","P01 CA066996","R01 CA259273","R01 CA176745","R01 CA204639","T32 HL007574","F32 CA250240","TRTH228","K08 CA252174"],"pubmed_authors":["Wen Y","Olsen SN","Hatton C","Crompton BD","Kirmani N","Ebert BL","Bourgeois W","Boileau M","Armstrong SA","Henrich JA","McGeehan GM","Perner F","Fischer ES","Perry JA","Sperling AS","Aubrey BJ","Martucci C","Apazidis AA","Pikman Y","Cutler JA","Nowak RP","Klega K","Donovan KA","Pollard JA","Wenge DV"],"additional_accession":[]},"is_claimable":false,"name":"Mezigdomide is effective alone and in combination with menin inhibition in preclinical models of KMT2A-r and NPM1c AML.","description":"<h4>Abstract</h4>Small molecules that target the menin-KMT2A protein-protein interaction (menin inhibitors) have recently entered clinical trials in lysine methyltransferase 2A (KMT2A or MLL1)-rearranged (KMT2A-r) and nucleophosmin-mutant (NPM1c) acute myeloid leukemia (AML) and are demonstrating encouraging results. However, rationally chosen combination therapy is needed to improve responses and prevent resistance. We have previously identified IKZF1/IKAROS as a target in KMT2A-r AML and shown in preclinical models that IKAROS protein degradation with lenalidomide or iberdomide has modest single-agent activity yet can synergize with menin inhibitors. Recently, the novel IKAROS degrader mezigdomide was developed with greatly enhanced IKAROS protein degradation. In this study, we show that","dates":{"release":"2024-01-01T00:00:00Z","publication":"2024 Apr","modification":"2026-06-02T07:57:28.215Z","creation":"2026-04-16T03:11:26.073Z"},"accession":"S-EPMC11033588","cross_references":{"pubmed":["38096371"],"doi":["10.1182/blood.2023021105"]}}