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Menin Inhibition in Acute Myeloid Leukemia: Pathobiology, Progress and Promise
1Department of Malignant Hematology, Moffitt Cancer Center, Tampa, FL 33612, USA.
Biomedicines
|January 28, 2026
Summary
Menin inhibitors show promise for treating Acute Myeloid Leukemia (AML) driven by specific genetic mutations like KMT2A and NPM1. These targeted therapies are transforming AML treatment for relapsed, refractory, and newly diagnosed patients.
Area of Science:
- Hematology
- Molecular Biology
- Oncology
Background:
- Acute Myeloid Leukemia (AML) is a diverse and aggressive cancer.
- A significant subset of AML is driven by overexpression of HOXA9 and MEIS1 oncogenic transcription factors.
- Key genetic abnormalities include KMT2A rearrangements, NPM1 mutations, and NUP98 rearrangements.
Purpose of the Study:
- To review the biology of KMT2A, NPM1, and HOX/MEIS1 pathways in leukemogenesis.
- To elucidate the role of the scaffolding protein menin in epigenetic regulation and malignant transformation.
- To evaluate the clinical efficacy and safety of menin inhibitors in AML.
Main Methods:
- Review of current literature on KMT2A, NPM1, HOX/MEIS1 pathways, and menin's role.
- Analysis of data on menin inhibitors as monotherapy and in combination treatments.
- Evaluation of clinical trial data, including efficacy and safety profiles.
Main Results:
- Menin plays a central role in the epigenetic regulation driving leukemogenesis in specific AML subsets.
- Menin inhibitors demonstrate significant therapeutic potential for AML with KMT2A, NPM1, or other relevant genetic anomalies.
- Emerging clinical data show promising efficacy and safety profiles for menin inhibitors.
Conclusions:
- Menin inhibitors are rapidly becoming a key therapeutic option for relapsed/refractory AML.
- These targeted agents are expected to play a significant role in newly diagnosed AML treatment paradigms.
- The development of menin inhibitors represents a major advancement in precision medicine for AML.
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