Npm1, also known as nucleophosmin 1, encodes a multifunctional protein with prominent nucleolar localization that shuttles between the nucleus and cytoplasm. It is involved in multiple cellular functions, such as ribosome biogenesis, chromatin remodeling, genomic stability, cell cycle progression, and apoptosis [4].

In acute myeloid leukemia (AML), Npm1 mutations are the most common genetic lesions, occurring in about one-third of adult cases. Mutant Npm1 proteins show aberrant cytoplasmic delocalization, and Npm1-mutated AML is recognized as a distinct entity in the WHO classification of hematopoietic neoplasms [1]. The cooperation between Npm1 and other mutations drives AML with different outcomes, and eradicating Npm1-mutated clones is important for achieving AML cure. Npm1-mutated cells rely on overexpression of HOX/MEIS1, which is related to the aberrant cytoplasmic localization of mutant Npm1 protein (Npm1c), and this may explain the promising response to novel agents like menin inhibitors and second-generation XPO1 inhibitors [2].

In conclusion, Npm1 is crucial for normal cellular functions, and its mutations are highly significant in AML. The study of Npm1-mutated AML using various models, including potentially KO/CKO mouse models (although not explicitly detailed in the references), helps to understand the disease mechanism and provides insights for targeted therapies in AML [1,2,3].