The Effect of Decitabine and ATRA on the Methylome in the AML cell line U-937

The combination of the demethylating agent Decitabine (DAC) and the retinoic acid ATRA has shown potent antileukemic action both in vitro and in vivo. The likely synergistic mechanism of action remains unknown. Both DAC and retinoid acids are known to affect methylation. DAC inhibits DNA-methyltransferases by covalent bonding, thereby causing demethylation after several replication cycles (Stresemann and Lyko, 2008). Depending on gene and entity, both demethylation (Das et al., 2010; Di Croce et al., 2002) as well as hypermethylation (Das et al., 2010) have been induced by treatment with retinoids. Therefore, a synergistic mechanism of action regarding the methylome to explain the combinatorial strong antileukemic effect of DAC+ATRA was investigated. A total of 24 samples was analzyed. These consisted of 3 treament modes (DAC, ATRA, DAC+ATRA) and an untreated control analyzed at 72 and 120 hours in technical triplicates.