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August 7, 2025Science Translational Medicine

Activation of a nongenetic AHR-ELMSAN1 axis optimizes BET-targeting therapy and suppresses leukemia stem cells in preclinical models

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Authors

XZXinyue ZhouSichuan UniversitySMSteven MoreiraUniversity of Colorado Anschutz Medical CampusCRCecilia RestelliUniversity Health Network

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Implication

Functional screening reveals AHR modulation improves responses to BET inhibitors in AML, suggesting new therapeutic strategies.

Key Points

  • Activation of the ahr pathway enhances sensitivity to bet inhibitors in acute myeloid leukemia, suppressing myc expression.
  • AHR activation synergizes with bet inhibitors, leading to significant inhibition of leukemia growth in preclinical models.
  • The study identified elmsan1 as a key target involved in histone deacetylation that impacts myc regulation and therapy response.
  • Combining AHR agonists with bet inhibitors effectively reduces leukemia stem cell frequency while sparing healthy blood stem cells.

Cite This Study

Zhou et al. (2025) studied this question.

synapsesocial.com/papers/689522069f4f1c896c42934chttps://doi.org/10.1126/scitranslmed.adn5400
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