High-altitude hypoxia exacerbates chemotherapy-induced myelosuppression by lowering serum G-CSF/GM-CSF and regulating apoptosis and proliferation
Abstract The unique hypoxic environment in high-altitude regions is increasingly drawing attention for its impact on the health of residents, particularly in patients post-chemotherapy. This study aimed to investigate the effects and potential mechanisms of high-altitude hypoxia on myelosuppression...
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| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Springer
2025-05-01
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| Series: | Discover Oncology |
| Subjects: | |
| Online Access: | https://doi.org/10.1007/s12672-025-02611-2 |
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| Summary: | Abstract The unique hypoxic environment in high-altitude regions is increasingly drawing attention for its impact on the health of residents, particularly in patients post-chemotherapy. This study aimed to investigate the effects and potential mechanisms of high-altitude hypoxia on myelosuppression following chemotherapy, with the goal of providing a theoretical basis for clinical treatment. A retrospective clinical study of 80 patients with breast cancer revealed that patients in the plateau exhibited a significantly higher incidence of grade 3 or higher neutropenia and any level of neutropenia post-chemotherapy than those in the plain, with propensity score matching (PSM) confirming these associations. Animal experiments revealed that high-altitude hypoxia reduced the white blood cell (WBC) count, granulocyte count, lymphocyte count, and number of bone marrow nucleated cells (BMNCs) in cyclophosphamide (CTX)-treated mice. Additionally, high-altitude hypoxia induced a significant reduction in the proliferation index and an elevation in apoptosis rates in BMNCs. High-altitude hypoxia also significantly reduced serum levels of granulocyte colony-stimulating factor (G-CSF) and granulocyte–macrophage colony-stimulating factor (GM-CSF). Transcriptomic analysis of BMNCs demonstrated that high-altitude hypoxia might modulate the hematopoietic function in CTX-induced myelosuppression mice through pathways related to hematopoiesis, such as porphyrin metabolism, hematopoietic cell lineage, ECM-receptor interaction, and PI3K-Akt signaling pathway. Our results suggest that high-altitude hypoxia exacerbates chemotherapy-induced myelosuppression, possibly through reducing the serum level of G-CSF/GM-CSF and regulating apoptosis and proliferation by PI3K-Akt signaling pathway, highlighting that cancer patients undergoing chemotherapy in hypoxic environments may require enhanced supportive care to mitigate these adverse effects. |
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| ISSN: | 2730-6011 |