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December 8, 2025Blood

Synergistic targeting of KMT2A-rearranged AML with combined LSD1 and menin inhibitors

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Authors

MTMina M. TayariFBFelipe BeckedorffDBDaniel Bilbao

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Overview

Observational analysis improved survival analysis in KMT2Ar AML, suggesting combined LSD1 and menin inhibitors may enhance treatment efficacy.

Key Points

  • Combination therapy significantly reduced leukemia burden and improved differentiation in KMT2Ar AML cells.
  • Response duration showed a lower IC50 for combined therapies, enhancing cell death beyond monotherapy effects.
  • High-throughput screening identified LSD1 as a critical target, validating synergy with menin through RNA-seq and other assays.
  • Findings indicate potential for combining epigenetic strategies in clinical trials targeting KMT2Ar AML populations.

Cite This Study

Tayari et al. (2025) studied this question.

synapsesocial.com/papers/69362f444fa91c937236d606https://doi.org/10.1182/blood-2025-3292
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Also Consider

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  1. 1Protein degradation of MYC/GSPT1 combined with menin inhibition overcomes resistance to menin inhibition in KMT2A-rearranged Acute Myeloid Leukemia2025 · 1 citations
  2. 2Preclinical activity of investigational menin inhibitor DSP-5336 (Enzomenib)-based combinations against MLL1-rearranged (MLL-r) or mutant-NPM1 AML models2025 · 1 citations
  3. 3The role of menin inhibitors in acute myeloid leukemia2025 · 2 citations
  4. 4Combination Strategies with Menin Inhibitors for Acute Leukemia2025 · 6 citations
  5. 5Therapeutic Implications of Menin Inhibitors in the Treatment of Acute Leukemia: A Critical Review2025 · 7 citations