Expression of the Hypoxia-Inducible Factors In the AML and MDS: Is Not Associated with the Von Hippel-Lindau Gene

Abstract 5114

The hypoxia-inducible factor (HIF) is a transcriptional factor with important roles in tumor biology, which activates transcription of genes encoding glucose transporters, glycolytic enzymes, and vascular endothelial growth factor. The VHL (von Hippel-Lindau) gene normally regulates ubiquitin mediated proteolysis of HIF-1a. VHL inactivation blocks HIF-1 proteolysis, resulting in increased HIF-1 expression. In the previous study, the expression of HIF-1a was detected in children ALL and NHL. To clarify the possible involvement of the HIF-1a and VHL gene in the development and progression of acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS), we analyzed the mutation and methylation of the VHL gene in 98 patients (54 AML and 44 MDS). The mutations in VHL gene was examined by direct exons sequence and the methylation status of the promoter region was determined using methylation-specific polymerase chain reaction (MSP). In addition, we examined the expression of HIF-1a in 44 of these patients (25 AML and 18 MDS) through the immunoblotting. VHL mutations were identified only in one patient with AML. However, no mutation was detected in the coding region of the VHL gene in MDS. Meanwhile the methylation of VHL gene was not found in the AML and MDS. But the expression of HIF-1a was found in 10 (66.7%) of 25 patients with AML and 5 (38.5%) of 18 patients with MDS. There is no significant correlation between the expression of HIF-1a and the VHL gene. Our primary date support that the HIF-1a may be involved in the development and progression of AML and MDS, but is not associated with the VHL gene.