Fig. 1

Analysis overview. A Overview of analysis steps based on DNA isolated from mononuclear cells from each pretreatment bone marrow aspirate from a subset of 155 AML samples derived from the AMLSG 12-09 trial. Global, genome-wide methylation status of a training set was analysed via MCIp followed by NGS-analysis on the HiSeq 2k platform. Differentially methylated regions were derived and ranked according to p-values and effect size. Methylation levels within a set of top regions were validated via 450k analysis at single CpG resolution and used to generate a classifier. B The validation cohort consisted of an independent subset of patients derived from the AMLSG 12-09 collective. Methylation status of the classifier contained CpGs was analysed via MassARRAY assay and used for validation. CR was defined as non-detectability of evidence for disease both cytomorphologically and via immunophenotyping in peripheral blood smear and bone marrow aspirate as well as via molecular genetics. AML acute myeloid leukemia; DMR differentially methylated regions; MCIp methyl-CpG immunoprecipitation; HiSeq 2k the HiSeq next-generation sequencing platform; NGS next generation sequencing; 450k Infinium® HumanMethylation450 Bead Chip; MassARRAY a benchtop multiplex genetic analyzer utilizing Matrix assisted laser desorption/ionization; time-of-flight mass spectrometry; std standard therapy arm; exp experimental therapy arm; CR complete response; RD refractory disease