A novel mechanism of NPM1 cytoplasmic localization in acute myeloid leukemia: the recurrent gene fusion NPM1–HAUS1

NPM1 heterozygous mutations are present in roughly a third of patients with acute myeloid leukemia (AML), making it one of the most frequent genomic alterations in these patients.1 The mutations are characterized by frameshift insertions in the region encoding the C-terminus of the protein, leading to the disruption of tryptophan residues 288 and 290 and the generation of an additional nuclear export signal (NES) motif, that ultimately leads to the cytoplasmic localization of the mutated NPM1 (NPM1m) as well as wild-type (WT) NPM1 proteins.2