ASXL1, a chaperone protein involved in guiding PRC2 to its target loci, is among the most frequently mutated genes in both myelodysplastic syndrome (MDS) and AML.78,84,85 Mutations in ASXL1 result in a truncated protein, reducing its ability to guide PRC2 to its target loci and resulting in a global reduction in H3K27me3 levels.84 As expected, genetic inactivation of Asxl1 in mouse hematopoietic cells leads to aberrant self-renewal and impaired differentiation.84,85. This evidence concerns the gene ASXL1 and acute myeloid leukemia.