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REVIEW

Clinical Integration of Menin Inhibitors in AML: Evolving Data and Therapeutic Perspectives

Tiffany Chen1, Grace Kim2, Yekta Rahimi3, Monisha Kamdar4, Eduardo Fernandez-Hernandez4, Karrune Woan4, Eric L. Tam4,*, George Yaghmour4
1 California University of Science and Medicine, Colton, CA 92324, USA
2 Keck School of Medicine of USC, University of Southern California, Los Angeles, CA 90033, USA
3 Department of Medicine, Keck School of Medicine of USC, Los Angeles, CA 90033, USA
4 Jane Ann Nohl Division of Hematology and Center for the Study of Blood Disease, USC Norris Comprehensive Cancer Center, Los Angeles, CA 90033, USA
* Corresponding Author: Eric L. Tam. Email: email

Oncology Research https://doi.org/10.32604/or.2025.072443

Received 27 August 2025; Accepted 30 December 2025; Published online 20 January 2026

Abstract

Acute myeloid leukemia (AML) remains a biologically heterogeneous disease with historically limited targeted therapies and poor outcomes. The development of menin inhibitors represents a promising shift, particularly for patients harboring KMT2A rearrangements (KMT2Ar) and NPM1 mutations (NPM1m). This manuscript reviews the molecular rationale of menin inhibition for aberrant homeobox/myeloid ectopic insertion site 1 (HOX/MEIS1)-driven gene expression and leukemogenesis, clinical trial outcomes, and safety data for menin inhibitors, with a focus on recently FDA-approved revumenib and several other agents in development, ziftomenib (KO-539), bleximenib (JNJ-75276617), and icovamenib (BMF-219). We also focused our discussion on future directions to include resistance mechanisms, biomarker identification and monitoring strategies, and combination therapies. Menin inhibition is now being clinically integrated into relapsed/refractory and frontline treatment settings.

Keywords

Menin; menin inhibitor; acute myeloid leukemia (AML); leukemia; revumenib; ziftomenib; bleximenib; icovamenib

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