Like in MLL-rearranged leukemias, aberrant expression of HOX genes and MEIS1 in hematopoietic progenitor cells is a distinct feature of NPM1c AML.36,37 Recent studies propose that the nuclear exporter Chromosomal Maintenance 1 (CRM1) binds the mutant NES to direct residual nuclear NPM1c to these loci, where it cooperates with the wildtype KMT2A complex (which is present at these loci in healthy HSCs) to directly bind chromatin and inappropriately upregulate transcription in committed progenitors in a manner akin to that of KMT2A-fusion proteins (Figure 1A). Here, KMT2A is linked to acute myeloid leukemia.