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December 8, 2025BloodOpen Access

DOT1L/menin inhibitors target replication fork plasticity and create novel vulnerability to PARP inhibitor in MLL-rearranged AML

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Authors

TFTsz Kan FungCDCyril DördelmannDPDanyue Peng

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Overview

Analysis reveals that DOT1L and menin inhibitors alter DNA damage response in acute myeloid leukemia, suggesting new therapeutic vulnerabilities to PARP inhibitors.

Key Points

  • Combination treatment using PARP inhibitors significantly increased DNA damage in acute myeloid leukemia cells.
  • Inhibitors showed a notable impact on cellular replication dynamics, shifting from repriming to fork reversal in MLL fusion cells.
  • Observational analysis across models of acute myeloid leukemia demonstrated significant tumor progression delays with combination therapies.
  • Therapeutic targeting of disrupted DNA repair pathways offers a novel approach to treating acute myeloid leukemia effectively.

Cite This Study

Fung et al. (2025) studied this question.

synapsesocial.com/papers/69362f4b4fa91c937236d763https://doi.org/10.1182/blood-2025-867
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Also Consider

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

  1. 1Replication fork remodeling is a therapeutic vulnerability in acute myeloid leukemia2025
  2. 2Synergistic targeting of KMT2A-rearranged AML with combined LSD1 and menin inhibitors2025
  3. 3Preclinical activity of investigational menin inhibitor DSP-5336 (Enzomenib)-based combinations against MLL1-rearranged (MLL-r) or mutant-NPM1 AML models2025 · 1 citations
  4. 4Therapeutic effect of menin inhibitors is reversible in AML treatment and could be enhanced by the targeting of differentiation associated chromatin complex2025
  5. 5Therapeutic Implications of Menin Inhibitors in the Treatment of Acute Leukemia: A Critical Review2025 · 7 citations