Nucleophosmin (NPM), one of the most abundant nucleolar proteins, has crucial functions in ribosome biogenesis, cell cycle control, and DNA-damage repair. In human cells, NPM occurs mainly in oligomers. It functions as a chaperone, undergoes numerous interactions and forms part of many protein complexes. Although NPM role in carcinogenesis is not fully elucidated, a variety of tumor suppressor as well as oncogenic activities were described. NPM is overexpressed, fused with other proteins, or mutated in various tumor types. In the acute myeloid leukemia (AML), characteristic mutations in NPM1 gene, leading to modification of NPM C-terminus, are the most frequent genetic aberration. Although multiple mutation types of NPM are found in AML, they are all characterized by aberrant cytoplasmic localization of the mutated protein. In this review, current knowledge of the structure and function of NPM is presented in relation to its interaction network, in particular to the interaction with other nucleolar proteins and with proteins active in apoptosis. Possible molecular mechanisms of NPM mutation-driven leukemogenesis and NPM therapeutic targeting are discussed. Finally, recent findings concerning the immunogenicity of the mutated NPM and specific immunological features of AML patients with NPM mutation are summarized.

Institute of Hematology and Blood Transfusion U Nemocnice 1 128 20 Prague 2 Czech Republic

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Correlation of p53 oligomeric status and its subcellular localization in the presence of the AML-associated NPM mutant

AML-Related NPM Mutations Drive p53 Delocalization into the Cytoplasm with Possible Impact on p53-Dependent Stress Response

NSC348884 cytotoxicity is not mediated by inhibition of nucleophosmin oligomerization

High PD-L1 Expression Predicts for Worse Outcome of Leukemia Patients with Concomitant NPM1 and FLT3 Mutations