2. Academic Validation
  3. GDF-15 upregulates the SLC7A11/GPX4 signaling axis and promotes mitoxantrone resistance in AML cells

GDF-15 upregulates the SLC7A11/GPX4 signaling axis and promotes mitoxantrone resistance in AML cells

  • Eur J Med Res. 2025 Jun 21;30(1):504. doi: 10.1186/s40001-025-02787-x.
Qian-Wei Lu 1,  Yang Liao 2
Affiliations

Affiliations

  • 1 Department of Oncology and Hematology, The Beibei Affiliated Hospital of Chongqing Medical University, The Ninth's People's Hospital of Chongqing, Chongqing, 400700, People's Republic of China.
  • 2 Department of Oncology and Hematology, University-Town Hospital of Chongqing Medical University, Chongqing, 401331, China. 800041@hospital.cqmu.edu.cn.
PMID: 40544302 DOI: 10.1186/s40001-025-02787-x
Abstract

Chemotherapy resistance poses a significant challenge in the initial treatment of acute myeloid leukemia (AML). Growth Differentiation Factor 15 (GDF-15) has been shown to play a critical role in Cancer progression; however, the potential mechanisms by which GDF-15 contributes to AML progression and chemotherapy resistance remain unclear. We found that M2 macrophages secrete high levels of GDF-15, promoting resistance of AML cells to mitoxantrone (MTX). Furthermore, we demonstrated that MTX induces downregulation of the SLC7A11/GPX4 signaling axis in AML cells, mediating Ferroptosis. GDF-15 enhances the expression of the SLC7A11/GPX4 axis, thereby inhibiting Ferroptosis in AML cells and contributing to drug resistance. In addition, GDF-15 mitigates the decline in mitochondrial membrane potential and mitochondrial quality induced by MTX. In vivo experiments indicate that blocking GDF-15 effectively enhances the sensitivity of AML cells to mitoxantrone by reducing the expression of the SLC7A11/GPX4 axis.

Keywords

Acute myeloid leukemia; Chemoresistance; Ferroptosis; GDF-15.

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