As a proof of principle and identifying disease specific targets, Wang et al. recently developed an iPSC based de novo model of AML progression by introducing mutations in genes encoding a transcriptional regulator (ASXL1) followed by RNA splicing regulator (SRSF2) and finally a signaling molecule (NRAS) using clustered regularly interspaced short palindromic repeats/Cas (CRISPR/Cas) (Figure 1) [80]. This evidence concerns the gene NRAS and acute myeloid leukemia.