The nucleophosmin (NPM1) gene encodes for the most abundant nucleolar protein. Thanks to its property to act as histone chaperone and to shuttle between the nucleus and cytoplasm, the NPM1 protein is involved in multiple cellular function that are here extensively reviewed and include the formation of the nucleolus through liquid-liquid phase separation, regulation of ribosome biogenesis and transport, control of DNA repair and centrosome duplication as well as response to nucleolar stress. NPM1 is mutated in about 30–35% of adult acute myeloid leukemia (AML). Due to its unique biological and clinical features, NPM1-mutated AML is regarded as a distinct leukemia entity in the WHO 5th edition and ICC classifications of myeloid malignancies. The NPM1 mutant undergoes changes at the C-terminus of the protein that leads to its delocalization in the cytoplasm of the leukemic cells. Here, we focus also on its biological functions discussing the murine models of NPM1 mutations and the various mechanisms that occur at cytoplasmic and nuclear levels to promote and maintain NPM1-mutated AML

核磷蛋白 （NPM1） 基因编码最丰富的核仁蛋白。由于其充当组蛋白伴侣并在细胞核和细胞质之间穿梭的特性，NPM1 蛋白参与多种细胞功能，这些功能在这里进行了广泛综述，包括通过液-液相分离形成核仁、调节核糖体生物发生和运输、控制 DNA 修复和中心体复制以及对核仁应激的反应。NPM1 在大约 30-35% 的成人急性髓性白血病 （AML） 中发生突变。由于其独特的生物学和临床特征，NPM1 突变的 AML 在 WHO 第 5 版和 ICC 髓系恶性肿瘤分类中被视为一种独特的白血病实体。NPM1 突变体在蛋白质的 C 端发生变化，导致其在白血病细胞的细胞质中脱离定位。在这里，我们还关注其生物学功能，讨论 NPM1 突变的小鼠模型以及在细胞质和细胞核水平发生的促进和维持 NPM1 突变 AML 的各种机制