The authors pinpoint loss-of-function mutations of KMT2C, encoding a component of the myeloid/lymphoid or mixed-lineage leukemia (MLL) chromatin remodelling complex, as a possible marker of chemorefractoriness, phenocopying chromosome 7q deletion, frequently observed also in adult higher-risk myelodysplastic syndromes (MDS) and secondary AML and found to be particularly susceptible to epigenetic therapies [18,19]. Here, KMT2A is linked to acute myeloid leukemia.