Methylation data of serially sorted primary AML patient blasts prior and after treatment with the DNMT inhibitor decitabine (DAC)

The therapeutic effect of DNA-hypomethylating agents (HMAs) in AML/MDS is discussed to be via its effects on aberrant gene silencing by reactivation (e.g. through promoter demethylation). While this has been broadly studied in cell line models, only very few studies have addressed the global effects of HMAs in primary blasts serially isolated from AML patients (pts) undergoing HMA treatment (Claus et al., Leuk. Res. 2013, Klco et al., Blood 2013, Welch et al., N. Engl. J. Med. 2016). We therefore conducted prospective serial methylome and transcriptome analyses on AML blasts from pts of the DECIDER trial (NCT00867672), hypothesizing that both random and non-random effects of the HMA may be observed in vivo. Genomic DNA was isolated with the DNeasy Blood & Tissue Kit (Qiagen, Hilden, Germany), bisulfite converted and hybridized to HumanMethylation450 BeadChip arrays (450K arrays; Illumina) according to the manufacturer’s instructions at the DKFZ Genomics and Proteomics Core Facilities (Heidelberg, Germany). To avoid a possible batch effect, samples were randomized across and within plates.