Bousquet, Marina <br/><br/>
NPM1-mutated acute myeloblastic leukemia 

 -  2023.<br/>							 
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<br/><br/> Acute myeloid leukemia (AML) with NPM1 mutations accounts for 30% of all AML cases and 50% of AML cases with normal karyotype. NPM1, or nucleophosmin, is a mainly nucleolar shuttle protein involved in many cellular processes, such as ribosome biogenesis, apoptosis, DNA repair, and centrosome duplication. In AML, numerous NPM1 mutations have been described, mainly in exon 12 of the NPM1 gene, and all of these mutations lead to a subcellular delocalization of the protein to the cytoplasm. This delocalization of NPM1 is the key event at the origin of tumor development. In recent years, advances in knowledge of NPM1-mutated AML have allowed a better understanding of the specificities of this pathology: namely, its mutual exclusion with other recurrent cytogenetic abnormalities, mutation present at relapse, aberrant localization of mutant NPM1 and wild-type NPM1, unique expression profile of homeobox genes, specific signatures of microRNA, and long non-coding RNA. Thus, since 2017, NPM1-mutated AML has been recognized as a distinct entity in the World Health Organization classification. This review provides an inventory of current knowledge on the oncogenic mechanisms mediated by mutated NPM1, with a particular focus on transcriptional dysregulation and the consequences of the delocalization of NPM1 and its partners. Technological advances, combined with a better understanding of the mode of action of mutated NPM1, make it possible to consider new therapeutic options in the treatment of NPM1-mutated AML.