High PD‑L1 expression drives glycolysis via an Akt/mTOR/HIF‑1α axis in acute myeloid leukemia

  • Authors:
    • Ping Ma
    • Mengtao Xing
    • Lijie Han
    • Silin Gan
    • Jie Ma
    • Feifei Wu
    • Yumin Huang
    • Yanli Chen
    • Wenliang Tian
    • Chao An
    • Hui Sun
    • Ling Sun
  • View Affiliations

  • Published online on: January 23, 2020     https://doi.org/10.3892/or.2020.7477
  • Pages: 999-1009
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Abstract

Acute myeloid leukemia (AML) is a hematological malignancy derived from immature myeloid cells, which have the characteristics of abnormal proliferation and differentiation. Glycolysis has been a popular topic of research in recent years, with increasing uptake and consumption of glucose. The present study aimed to investigate the glycolysis of tumor cells in patients with AML; in particular, how programmed cell death 1 ligand 1 (PD‑L1) regulates tumor cells glycolysis using real time PCR (RT‑PCR), western blotting and flow cytometry. PD‑L1 high expression predicted poor outcome in patients with AML in the public database Gene Expression Profiling Interactive Analysis. PD‑L1 expression was decreased in the samples from patients with AML with complete remission compared to that in patients with relapsed or refractory AML. In AML cell lines, glycolysis‑associated genes ALDOA, PGK1, LDHA and HK2 were highly expressed in a PD‑L1 high‑expressed cell line. Overexpressed PD‑L1 enhanced glucose consumption and the extracellular acidification rate, accompanied by decreased apoptosis and accumulation of cells in the S phase. In contrast, the apoptosis rate of tumor cells and the percentage of cells in the S phase were significantly increased following PD‑L1 knockdown in the THP1 cell line. HK2 and LDHA expression decreased after AML tumor cells were treated with Akt inhibitor or rapamycin. In addition, the PD‑L1‑overexpressed cell line (PD‑L1‑OV) MOLM‑13 exhibited rapid tumor progression. Glycolysis‑associated genes were highly expressed in tumor tissues of PD‑L1‑OV MOLM‑13, with increased Ki67. Based on these findings, PD‑L1 may be considered as a suitable marker for prognosis and treatment in the clinical setting.
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March-2020
Volume 43 Issue 3

Print ISSN: 1021-335X
Online ISSN:1791-2431

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Spandidos Publications style
Ma P, Xing M, Han L, Gan S, Ma J, Wu F, Huang Y, Chen Y, Tian W, An C, An C, et al: High PD‑L1 expression drives glycolysis via an Akt/mTOR/HIF‑1α axis in acute myeloid leukemia. Oncol Rep 43: 999-1009, 2020.
APA
Ma, P., Xing, M., Han, L., Gan, S., Ma, J., Wu, F. ... Sun, L. (2020). High PD‑L1 expression drives glycolysis via an Akt/mTOR/HIF‑1α axis in acute myeloid leukemia. Oncology Reports, 43, 999-1009. https://doi.org/10.3892/or.2020.7477
MLA
Ma, P., Xing, M., Han, L., Gan, S., Ma, J., Wu, F., Huang, Y., Chen, Y., Tian, W., An, C., Sun, H., Sun, L."High PD‑L1 expression drives glycolysis via an Akt/mTOR/HIF‑1α axis in acute myeloid leukemia". Oncology Reports 43.3 (2020): 999-1009.
Chicago
Ma, P., Xing, M., Han, L., Gan, S., Ma, J., Wu, F., Huang, Y., Chen, Y., Tian, W., An, C., Sun, H., Sun, L."High PD‑L1 expression drives glycolysis via an Akt/mTOR/HIF‑1α axis in acute myeloid leukemia". Oncology Reports 43, no. 3 (2020): 999-1009. https://doi.org/10.3892/or.2020.7477