Effects of hypoxia on the proliferation and genomic methylation of acute myeloid leukemia bone marrow mononuclear cells
Objective To investigate the effects of hypoxia on the proliferation and genomic methylation of bone marrow mononuclear cells in patients with acute myeloid leukemia(AML).Methods The bone marrow fluid was collected from newly diagnosed AML patients,mononuclear cells were isolated.Cells were treated with different concentrations of oxygen(oxygen content 21%,3%,and 1%,respectively)for 24,48,and 72 h,with normal oxygen(oxygen content 21%)as the control.The effects of hypoxia on the proliferation,metabolism,and apoptosis of bone marrow mononuclear cells were analyzed using CCK-8 method,lactate dehydrogenase detection,and Hoechst 33258 staining.The 5-hydroxymethylcytosine(5-hmC)and 5-methylcytosine(5-mC)detection kits were used to detect the 5-hmC and 5-mC contents in the genome of AML cells,and the impact of hypoxia on the methylation status of the genome was analyzed.Results As the degree of hypoxia increased,the proliferative activity and metabolic activity of AML cells were increased,while apoptosis was decreased,with a statistically significant difference(P<0.05).As the degree of hypoxia increased,the content of 5-hmC in the cell genome was increased,while the content of 5-mC was decreased(P<0.05).The proliferation and demethylation of cells were strongest when the cells were cultured at a concentration of 1%O2 for 48 h.Conclusion Hypoxia promotes the proliferation and metabolism of AML bone marrow mononuclear cells,inhibits cell apoptosis,and promotes cell genome demethylation.
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