Epigenetic regulation of PAX5 expression in acute T-cell lymphoblastic leukemia.

The analysis of genomic alterations in acute lymphoblastic leukemia (ALL) has provided new insights for prognosis and possible targets of novel therapies. In T-ALL the role of molecular abnormalities has still to be determined. Deregulated promoter hypermethylation of critical genes like PAX5 may have a significant impact on the course of ALL. Samples derived from 75 patients with ALL (B-ALL = 24, T-ALL = 51) and from healthy volunteers were analyzed. PAX5 expression was assessed by micro-array analysis (HG-U133plus 2.0) and correlated with promoter CpG island methylation of PAX5 using a pyrosequencing approach. The analyzed CpG marks in the promoter region of PAX5 were completely and uniformly unmethylated in the control group of healthy individuals. The T-ALL cases featured even higher methylation levels (median: 20%) with a strong variation of values of up to 85% methylation. Analysis of the association of altered methylation levels with gene expression data indicated a differential epigenetic regulation of PAX5 through promoter methylation which may contribute to the pathogenesis of this disease.