Promoter hyper-methylation of tumor suppressor gene is another important epigenetic abnormality of HL and two important tumor suppressor genes of HL (PU.1 and KLF4) have been found to be down-regulated through methylation changes in the promoter region in cell lines and tumor cells of HL, besides, the down regulation of KLF4 gene is related with characteristic phenotype of HL [8, 9]. This evidence concerns the gene SPI1 and neoplasm.