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December 8, 2025BloodOpen Access

Targeting BRD9 in KMT2A-rearranged Acute Myeloid Leukemia to circumvent MEN1 inhibitor resistance

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Authors

DWDaniela V. Wenge

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Overview

Observational analysis shows that targeting BRD9 reduces resistance in AML cells with KMT2A rearrangements, suggesting a new therapeutic approach.

Key Points

  • KMT2A-rearranged acute myeloid leukemia exhibits resistance to MEN1 inhibitors, necessitating alternative therapies.
  • Chemical depletion of BRD9 led to significant reductions in cell viability and enhanced myeloid differentiation as evidenced by CD11b expression.
  • Chromatin accessibility and gene expression profiling indicated that BRD9 impacts transcription factors like IRF8 and MYC in AML cells.
  • These findings suggest targeted anti-BRD9 therapy may effectively treat KMT2Ar AML even after MEN1 inhibitor resistance.

Cite This Study

Daniela V. Wenge (2025) studied this question.

synapsesocial.com/papers/69362f604fa91c937236dcb6https://doi.org/10.1182/blood-2025-1463
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Also Consider

Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context:

  1. 1The KMT2A-PTD oncoprotein depends on ENL but not menin to drive AML gene expression2025 · 1 citations
  2. 2Protein degradation of MYC/GSPT1 combined with menin inhibition overcomes resistance to menin inhibition in KMT2A-rearranged Acute Myeloid Leukemia2025 · 1 citations
  3. 3HMGA1 chromatin regulators drive transcriptional networks governing cell cycle progression, immune escape, and menin-inhibitor resistance in KMT2A-r Acute Myeloid Leukemia2025
  4. 4A perturb-seq map of a differentiation hub reveals synergistic vulnerabilities in KMT2A-rearranged AML2025
  5. 5Therapeutic Implications of Menin Inhibitors in the Treatment of Acute Leukemia: A Critical Review2025 · 6 citations