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September 5, 2026Experimental & Molecular MedicineOpen Access

Bone marrow stromal cells promote chemoresistance in acute myeloid leukaemia through P2RX7-mediated antioxidant defence

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Authors

RYRuolan YouXWXiaoting WangXZXiaoming Zheng

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Overview

Experimental study demonstrates bone marrow stromal cells drive chemoresistance in acute myeloid leukaemia, highlighting P2RX7 as a therapeutic target.

Key Points

  • To elucidate how bone marrow stromal cells promote chemoresistance and antioxidant adaptations in acute myeloid leukaemia.
  • Investigated the expression and signaling role of the purinergic receptor P2RX7 in acute myeloid leukaemia (AML) cells co-cultured with bone marrow stromal cells (BMSCs).
  • Characterized downstream intracellular pathways, including calcium influx, mitochondrial stress, PGAM5-mediated ROS signaling, and Keap1–Nrf2 complex regulation.
  • BMSCs induced P2RX7 upregulation in AML cells to confer chemoresistance, whereas pharmacological or genetic blockade of P2RX7 successfully restored chemosensitivity.
  • P2RX7 activation drove mitochondrial calcium overload and engaged mitochondrial PGAM5 to disrupt Keap1–Nrf2 interaction, leading to Nrf2 stabilization and enhanced antioxidant defenses.

Cite This Study

You et al. (2026) studied this question.

synapsesocial.com/papers/6a9bd4726b95aff0620ec324https://doi.org/10.1038/s12276-026-01839-4
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Also Consider

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