Hypermethylation of the pax5 gene promoter and its implication in the pathogenesis of multiple myeloma

Abstract EN

Human multiple myeloma (MM) is a monoclonal proliferative disorder of plasma cells homing to the bone marrow.

Successful treatment solicits proper diagnosis and good understanding of pathophysiology.

The oncogenic event in human MM is still unknown.

It has been previously shown that the paired box-containing (PAX5) gene, which is important for B cell development, is completely silenced in human MM.

In this study we tried to clarify the mechanism of silencing of the PAX5 gene.

Genetic analysis of the coding region and promoter by Southern blot analysis did not show gross structural abnormalities in human MM cell lines when compared to PAX5 expressing B cells.

Several transcription factors like lkaros-l (Ik-1), and SRY-related high mobility group (HMG) box (SOX4 and SOX5) showed similar expression pattern in B cells and MM cells.

This led to the suggestion that epigenetic factors could be involved in PAX5 silencing.

Examination of the methylation pattern in PAX5 promoter revealed some areas of hypermethylation in methylation sensitive Southern blot analysis.

Moreover, treatment of MM cell lines by methylation blocking cytidine analogue 5-Aza-2' deoxycytidine (5-Aza-2 '-dC) could restore the expression of PAX5 gene.

We postulate that hypermethylation of the PAX5 gene promoter may be responsible for its silencing in human MM.

It has been proposed that PAX5 gene silencing could be related to the oncogenesis of human MM