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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| Format: | Article |
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Springer
2025-05-01
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| Series: | Discover Oncology |
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| Online Access: | https://doi.org/10.1007/s12672-025-02611-2 |
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| author | Jing Shi Fuxing Zhao Tianlei Qiu Dengfeng Ren Zitao Li Junli Ma Jiuda Zhao |
| author_facet | Jing Shi Fuxing Zhao Tianlei Qiu Dengfeng Ren Zitao Li Junli Ma Jiuda Zhao |
| author_sort | Jing Shi |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-3cf407af0a2d4600b6a84fdb5d199fd6 |
| institution | OA Journals |
| issn | 2730-6011 |
| language | English |
| publishDate | 2025-05-01 |
| publisher | Springer |
| record_format | Article |
| series | Discover Oncology |
| spelling | doaj-art-3cf407af0a2d4600b6a84fdb5d199fd62025-08-20T02:03:36ZengSpringerDiscover Oncology2730-60112025-05-0116111810.1007/s12672-025-02611-2High-altitude hypoxia exacerbates chemotherapy-induced myelosuppression by lowering serum G-CSF/GM-CSF and regulating apoptosis and proliferationJing Shi0Fuxing Zhao1Tianlei Qiu2Dengfeng Ren3Zitao Li4Junli Ma5Jiuda Zhao6School of Clinical Medicine of Qinghai University, Affiliated Hospital of Qinghai UniversityBreast Disease Diagnosis and Treatment Center of Affiliated Hospital of Qinghai University, Affiliated Cancer Hospital of Qinghai UniversityBreast Disease Diagnosis and Treatment Center of Affiliated Hospital of Qinghai University, Affiliated Cancer Hospital of Qinghai UniversityBreast Disease Diagnosis and Treatment Center of Affiliated Hospital of Qinghai University, Affiliated Cancer Hospital of Qinghai UniversityBreast Disease Diagnosis and Treatment Center of Affiliated Hospital of Qinghai University, Affiliated Cancer Hospital of Qinghai UniversityAffiliated Hospital of Jining Medical UniversityBreast Disease Diagnosis and Treatment Center of Affiliated Hospital of Qinghai University, Affiliated Cancer Hospital of Qinghai UniversityAbstract 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.https://doi.org/10.1007/s12672-025-02611-2High-altitude hypoxiaChemotherapyMyelosuppressionHematopoietic function |
| spellingShingle | Jing Shi Fuxing Zhao Tianlei Qiu Dengfeng Ren Zitao Li Junli Ma Jiuda Zhao High-altitude hypoxia exacerbates chemotherapy-induced myelosuppression by lowering serum G-CSF/GM-CSF and regulating apoptosis and proliferation Discover Oncology High-altitude hypoxia Chemotherapy Myelosuppression Hematopoietic function |
| title | High-altitude hypoxia exacerbates chemotherapy-induced myelosuppression by lowering serum G-CSF/GM-CSF and regulating apoptosis and proliferation |
| title_full | High-altitude hypoxia exacerbates chemotherapy-induced myelosuppression by lowering serum G-CSF/GM-CSF and regulating apoptosis and proliferation |
| title_fullStr | High-altitude hypoxia exacerbates chemotherapy-induced myelosuppression by lowering serum G-CSF/GM-CSF and regulating apoptosis and proliferation |
| title_full_unstemmed | High-altitude hypoxia exacerbates chemotherapy-induced myelosuppression by lowering serum G-CSF/GM-CSF and regulating apoptosis and proliferation |
| title_short | High-altitude hypoxia exacerbates chemotherapy-induced myelosuppression by lowering serum G-CSF/GM-CSF and regulating apoptosis and proliferation |
| title_sort | high altitude hypoxia exacerbates chemotherapy induced myelosuppression by lowering serum g csf gm csf and regulating apoptosis and proliferation |
| topic | High-altitude hypoxia Chemotherapy Myelosuppression Hematopoietic function |
| url | https://doi.org/10.1007/s12672-025-02611-2 |
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