Hypermethylation of the PAX 5 gene promoter and its implication in the pathogenesis of multiple myeloma

ABSTRACT

This study aimed to clarify the mechanism of silencing of the PAX5 gene. The genetic analysis of the coding region and promoter by southern blot analysis did not show growth structural abnormalities in human multiple myeloma [MM] cell lines when compared with PAX5 expressing B cells. Several transcription factors like Ikaros-1 [IK-1] and SRY-related high mobility group [HMG] box [SOX4 and SOX5] showed a similar expression pattern in B cells and MM cells. Therefore, it was suggested that epigenetic factors could be involved in PAX5 silencing. The examination of the methylation pattern in PAX5 promoter revealed some areas of hypermethylation in methylation sensitive Southern blot analysis. Moreover, the treatment of MM cell lines by methylation blocking cytidine analogue 5-aza-2 deoxycytidine [5-aza-2dC] could restore the expression of PAX5 gene. It was postulated that hypermethylation of the PAX5 gene promoter may be responsible for its silencing in human MM. It was proposed that PAX5 gene silencing could be related to the oncogenesis of human MM