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December 8, 2025Blood

Ferroptosis escape in AML stem cells uncovered by single-cell profiling and reversed by STAT3/NRF2 inhibition

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Authors

RGRitu GuptaVSVivek SinghRSRomila Singh

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Overview

Single-cell profiling reveals the role of ferroptosis and transcription factors in leukemic stem cells' chemoresistance.

Key Points

  • This research aims to understand the mechanisms of ferroptosis evasion in AML stem cells and how targeting specific pathways can enhance treatment.
  • Utilized single-cell multi-omics approach to profile leukemic stem cells and normal hematopoietic stem cells.
  • Conducted differential gene expression analysis comparing AML LSCs with healthy HSCs.
  • Analyzed the effects of STAT3 and NRF2 inhibition on ferroptosis pathways using various assays.
  • Identified altered gene expression linked to ferroptosis, including significant changes in FTH1 and GPX4.
  • Demonstrated that inhibiting STAT3 can reduce ROS levels but may counteract ferroptosis due to NRF2 upregulation.
  • Combination treatment with dual inhibitors enhanced ferroptosis and reduced proliferation of LSCs, suggesting a novel therapeutic strategy.

Cite This Study

Gupta et al. (2025) studied this question.

synapsesocial.com/papers/69362f604fa91c937236dcd8https://doi.org/10.1182/blood-2025-1487
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Also Consider

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

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