HIF-α Promotes Chronic Myelogenous Leukemia Cell Proliferation by Upregulating p21 Expression

We sought to determine the expression levels of hypoxia-inducible factor-1 alpha (HIF-1 alpha) in the bone marrow chronic myelogenous leukemia (CML) patients. We also tried to determine the roles HIF-1 alpha in the proliferation of CML cells by small interfering RNA (siRNA) knockdown. Real-time PCR was performed to determine the expression levels of HIF-1 alpha in the bone marrows of CML patients and healthy volunteers. HIF-1 alpha knockdown by siRNA in K562 cells was confirmed by RT-PCR. Proliferation and colony formation of the treated cells were determined by CCK8 after HIF-1 alpha knockdown. RT-PCR and western blotting were performed to detect mRNA and protein levels of p21 and p53 in K562 cells. HIF-1 alpha mRNA expression in the bone marrow of CML patients was significantly higher than that in the control, which was statistically significant (P < 0.05). HIF-1 alpha knockdown dramatically reduced the proliferation of K562 cells, which was also statistically significant (P < 0.05). HIF-1 alpha knockdown markedly reduced the colony formation ability of K562 cells, which was also statistically significant (P < 0.05). The mRNA and protein expression of p21 were significantly reduced in K562 cell after HIF-1 alpha knockdown with affecting the mRNA and protein levels of p53. HIF-alpha promotes chronic CML cell proliferation by up-regulating p21 expression.