Effect of Metabolic Reprogramming on the Biological Activity of Acute Myeloid Leukemia Cells

ABSTRACT

Metabolic reprogramming of acute myeloid leukemia (AML) cell lines has been described as a compensatory adaptation to fulfill their energy requirements for its rapid proliferation. In this study,we examined the role of the glutamine (Gln) removal or inhibition of glutaminase by GLS inhibitor bis-2-(5-phenylacetamido-1, 2, 4-thiadiazol- 2-yl) ethyl sulfide(BPTES) in AML cell lines SKM-1 to Observe whether it has an effect on the biological activity of SKM-1 cells. Our results indicated that inhibit glutamine uptake or utilization can inhibit cell growth and induce apoptosis in AML. we used Long non-coding RNAs (LncRNAs) Gene Microarray to analyze gene expression after Gln deprivation treatment. We found that the expression of MT2A, MT1X, MT3, MT1H, MT1F and MT1E in the metallothionein (MT) gene family was significantly upregulated and the expression of AGT、CSF1R、PAK7、MYCN、ARG1 was significantly downregulated . We further analysed the expression of MT isogenes by quantitative real-time PCR (RT-PCR). The results showed that the gene expression of the MT gene family was upregulated, consistent with the results of the Gene Microarray. These findings indicate that metallothionein may play an important role in the glutamine metabolic pathway of AML cells. metformin, a commonly used antidiabetic drug, play an important role in Glucose Metabolism.We observed that Metformin alone exhibited a dose-dependent anti-leukemic activity in SKM-1 cell lines and its anti-leukemic activity was enhanced when used in combination with Gln deprivation or Cytarabine. These findings show that Gln deprivation or Metformin enhance the sensitivity of SKM-1 cell line to chemotherapeutic agents. Taken together , targeting amino acid metabolism and glucose metabolism are promising new therapeutic strategies to enhance the efficacy of chemotherapeutic agents in AML.

Conflict of interest

No relevant conflicts of interest to declare.

Acknowledgments:

Tongyuan Liu analyzed the data, plotted the tables and figures and wrote the paper; Dengju Li designed projects and revised the paper. This work was supported by the National Natural Science Foundation of China (Grant no. 81770168).