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

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.