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Hypoxic exposure activates the B cell‑specific Moloney murine leukaemia virus integration site 1/PI3K/Akt axis and promotes EMT in leukaemia stem cells

  • Authors:
    • Mingyan Jiang
    • Guoqian He
    • Jianhua Li
    • Jinrong Li
    • Xia Guo
    • Ju Gao
  • View Affiliations / Copyright

    Affiliations: Department of Pediatric Hematology and Oncology, West China Second University Hospital of Sichuan University, Chengdu, Sichuan 610041, P.R. China, Key Laboratory of Birth Defects and Related Diseases of Women and Children, Sichuan University, Ministry of Education, Chengdu, Sichuan 610041, P.R. China
    Copyright: © Jiang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 98
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    Published online on: December 8, 2020
       https://doi.org/10.3892/ol.2020.12359
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Abstract

Acute myeloid leukemia (AML) is a malignant tumor of the immature myeloid hematopoietic cells in the bone marrow. Disease recurrence driven by leukaemia stem cells (LSCs), a sub‑population of leukaemia cells presenting self‑renewal capacity and differentiation potential, is a major problem in the treatment of AML. Although a hypoxic microenvironment is considered to promote AML malignant behaviours and is considered a potential therapeutic target, the effect of hypoxic stimulation of LSCs is still largely unknown. Therefore, the present study analysed the effects of hypoxia on the malignant behaviours of LSCs. Hypoxia exposure upregulated hypoxia‑inducible factor (HIF)‑1α, which upregulated the transcription of B cell‑specific Moloney murine leukaemia virus integration site 1 (BMI‑1). Hypoxia exposure also activated the PI3K/Akt pathway and promoted the epithelial mesenchymal transition (EMT) in LSCs via hypoxia‑mediated activation of HIF‑1α. BMI‑1 served an important role in the hypoxia‑induced activation of the PI3K/Akt pathway and the promotion of EMT. Hypoxia exposure promoted chemoresistance against cytarabine arabinoside by inducing HIF‑1α, thus activating the transcriptional activity of HIF‑1α. Knockdown of BMI‑1 disrupted hypoxia‑induced chemoresistance in LSCs, indicating that HIF‑1α‑induced BMI‑1 has a role in hypoxia‑promoted malignant behaviours. Furthermore, it was demonstrated that induced BMI‑1 inhibits the self‑renewal capacity in LSCs under hypoxic conditions. The present study provides in vitro evidence demonstrating that hypoxia exposure regulates LSCs by activating HIF‑1α/BMI‑1 signalling, in turn modulating PI3K/Akt signalling and EMT. These results highlight potentially novel therapeutic targets of LSCs to improve the treatment of AML.
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Copy and paste a formatted citation
Spandidos Publications style
Jiang M, He G, Li J, Li J, Guo X and Gao J: Hypoxic exposure activates the B cell‑specific Moloney murine leukaemia virus integration site 1/PI3K/Akt axis and promotes EMT in leukaemia stem cells. Oncol Lett 21: 98, 2021.
APA
Jiang, M., He, G., Li, J., Li, J., Guo, X., & Gao, J. (2021). Hypoxic exposure activates the B cell‑specific Moloney murine leukaemia virus integration site 1/PI3K/Akt axis and promotes EMT in leukaemia stem cells. Oncology Letters, 21, 98. https://doi.org/10.3892/ol.2020.12359
MLA
Jiang, M., He, G., Li, J., Li, J., Guo, X., Gao, J."Hypoxic exposure activates the B cell‑specific Moloney murine leukaemia virus integration site 1/PI3K/Akt axis and promotes EMT in leukaemia stem cells". Oncology Letters 21.2 (2021): 98.
Chicago
Jiang, M., He, G., Li, J., Li, J., Guo, X., Gao, J."Hypoxic exposure activates the B cell‑specific Moloney murine leukaemia virus integration site 1/PI3K/Akt axis and promotes EMT in leukaemia stem cells". Oncology Letters 21, no. 2 (2021): 98. https://doi.org/10.3892/ol.2020.12359
Copy and paste a formatted citation
x
Spandidos Publications style
Jiang M, He G, Li J, Li J, Guo X and Gao J: Hypoxic exposure activates the B cell‑specific Moloney murine leukaemia virus integration site 1/PI3K/Akt axis and promotes EMT in leukaemia stem cells. Oncol Lett 21: 98, 2021.
APA
Jiang, M., He, G., Li, J., Li, J., Guo, X., & Gao, J. (2021). Hypoxic exposure activates the B cell‑specific Moloney murine leukaemia virus integration site 1/PI3K/Akt axis and promotes EMT in leukaemia stem cells. Oncology Letters, 21, 98. https://doi.org/10.3892/ol.2020.12359
MLA
Jiang, M., He, G., Li, J., Li, J., Guo, X., Gao, J."Hypoxic exposure activates the B cell‑specific Moloney murine leukaemia virus integration site 1/PI3K/Akt axis and promotes EMT in leukaemia stem cells". Oncology Letters 21.2 (2021): 98.
Chicago
Jiang, M., He, G., Li, J., Li, J., Guo, X., Gao, J."Hypoxic exposure activates the B cell‑specific Moloney murine leukaemia virus integration site 1/PI3K/Akt axis and promotes EMT in leukaemia stem cells". Oncology Letters 21, no. 2 (2021): 98. https://doi.org/10.3892/ol.2020.12359
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