核磷蛋白(NPM1)基因的体细胞突变在新发急性髓系白血病(AML)中大约发生在30%左右的病例中，并且在正常核型(NK)的AML中相对富集。早期的世界卫生组织(WHO)分类方案将NPM1突变的AML识别为AML的独特亚型，而最新的WHO和国际共识分类(ICC)现在将NPM1突变视为AML定义，尽管在不同的爆发计数阈值下。NPM1突变负荷与疾病状态密切相关，特别是在治疗后的情况下，因此用于检测突变等位基因的高灵敏度方法已被证明对最小/可测量残留疾病(MRD)监测非常有用。传统上，MRD状态通过多参数流式细胞术(MFC)和/或分子诊断技术来测量，尽管最近的数据表明，在这种AML亚型中，MFC数据可能更具挑战性。需要注意的是，MRD状态并不能预测所有情况下的患者预后，因此可能需要深入了解MRD的生物学意义。最近的研究证实，NPM1突变细胞依赖于HOX/MEIS1的过度表达，这取决于突变NPM1蛋白(NPM1c)的异常胞质定位的存在；这种生物学现象可能解释了对新型药物，包括menin抑制剂和第二代XPO1抑制剂的有望反应。在本篇综述中，将讨论围绕NPM1突变AML的最新进展以及需要进一步研究的开放问题，由作者发表。S. Karger AG, Basel出版。

Somatic mutations in the nucleophosmin (NPM1) gene occur in approximately 30% of de novo acute myeloid leukemias (AML), and are relatively enriched in normal karyotype (NK) AMLs. Earlier World Health Organization (WHO) classification schema recognized NPM1-mutated AMLs as a unique subtype of AML, while the latest WHO and International Consensus Classification (ICC) now consider NPM1 mutations as AML-defining, albeit at different blast count thresholds. NPM1 mutational load correlates closely with disease status, particularly in the post-therapy setting, and therefore high sensitivity-based methods for detection of the mutant allele have proven useful for minimal/measurable residual disease (MRD) monitoring. MRD status has been conventionally measured by either multiparameter flow cytometry (MFC) and/or molecular diagnostic techniques, although recent data suggest that MFC data may be potentially more challenging to interpret in this AML subtype. Of note, MRD status does not predict patient outcome in all cases, and therefore a deeper understanding of the biological significance of MRD may be required. Recent studies have confirmed that NPM1-mutated cells rely on overexpression of HOX/MEIS1, which is dependent on the presence of the aberrant cytoplasmic localization of mutant NPM1 protein (NPM1c); this biology may explain the promising response to novel agents, including menin inhibitors and second-generation XPO1 inhibitors. In this review, these and other recent developments around NPM1-mutated AML, in addition to open questions warranting further investigation, will be discussed.The Author(s). Published by S. Karger AG, Basel.