Influence of clofarabine on transcriptional activity of PTEN, APC, RARB2, ZAP70 genes in K562 cells.

In this study, the effect of clofarabine, a new generation 2'-deoxyadenosine analogue, on promoter methylation and transcriptional activity of selected genes (PTEN, APC, RARB2, ZAP70) in K562 cells was assessed.,Promoter methylation was estimated using methylation-sensitive restriction analysis. The mRNA level of the genes was measured with real-time PCR.,The inhibitory cytostatic index (IG(50)) for clofarabine in K562 cells cultured for 72 (or 96) h was 8 nM. The drug (20 nM) caused: (i) potent diminution in methylation of PTEN promoter, moderate methylation reduction of APC and RARB2 promoters, and complete methylation of ZAP70 promoter; (ii) significant stimulation of PTEN, APC, RARB, and p21 mRNA expression and (iii) decline in mRNA level of ZAP70 and DNMT1 genes.,The results indicated that clofarabine is involved in epigenetic regulation of transcriptional activity of the tested tumour suppressor genes and genes encoding proteins involved in DNA methylation process.