Effect of hypoxia-inducible factor 1α in inhibiting cellular proliferation of acute myeloid leukemia carrying C-kit mutation

Objective To investigate the effect of silencing of hypoxia inducible factor 1α (HIF1α) on the expression of C-kit gene and cellular malignant biological behavior in t(8;21) AML carrying C-kit gene mutation. Methods Two t(8;21) AML cell lines carrying C-kit gene mutation,Kasumi-1 and SKNO-1,were respectively treated with different concentration of HIF1α specific inhibitors echinomycin (1 nmol/L,5 nmol/L,10 nmol/L,20 nmol/L,30 nmol/L,respectively).The cells were harvested at 24 hours after treatment,and those treated with dimethyl sulfoxide were selected as control group.Real-time quantitative RT-PCR was used to detect the HIF1α and C-kit gene mRNA expression levels,Western blot for protein expression levels,AnnexinV-PI double staining followed by flow cytometry for cellular apoptosis,and Colony-forming assay for cellular proliferation in vitro. Results Echinomycinsignificantly inhibited the mRNA and protein expression levels of HIF1α and C-kit genes in Kasumi-1 and SKNO-1 cells with a concentration-dependent manner.The proliferation of both cell lines was inhibited and cellular apoptosis increased. Conclusion Targeted inhibition of HIF1α using echinomycin can inhibit the proliferation of t(8;21) AML cells carrying C-kit gene mutation by down-regulating the expression of C-kit,which is related to the increased cellular apoptosis caused by echinomycin.