High-throughput genomic analysis using array- and sequencing-based methods. (A) For P08, EZH2 I122T appears to have the highest but unexpected VAF (>>50%), which can be explained by the presence of a telomeric copy number neutral UPD of chromosome 7q as identified by single nucleotide polymorphism (SNP)-array analysis (B). (C) Experimental setup of xenotransplantation for P08. After 14 weeks of long-term engraftment, human CD45⁺ (hCD45⁺) cells were FACS sorted for subsequent mutational analysis (exemplarily shown for NSGS mouse #6). (D) Three independent xenografts from P08 were subjected to quantitative profiling of mutations detected in primary BM and revealed exclusive expansion of an ancestral ASXL1-only mutated clone (see supplemental Figure 1D for mutational raw data). (E) Reconstructed mutational hierarchy for P08. Error bars indicate standard deviation (SD). I.F., intrafemoral; SSC-A, side scatter area.