It has been clearly demonstrated that the acquired NES of NPMc+ is able to form a complex with CRM1 in vitro [25, 32], and that both factors (impaired nucleolar retention due to unfolding, and acquired NES activity) jointly contribute to aberrant cytoplasmic accumulation of mutant NPM in AML [28, 33]. Here, NPM1 is linked to acute myeloid leukemia.