急性髓系白血病（AML）是一种具有异质分子结构的侵袭性血液恶性肿瘤。在儿科领域，NUP98 基因是染色体重排的常见目标，与不同 AML 亚型的不良预后和不良治疗结果相关。这些易位将 NUP98 与多种伙伴基因融合，从而产生具有新功能的融合蛋白。 NUP98 融合癌蛋白诱导异常的生物分子凝聚、异常的基因表达程序和重新连接的蛋白质相互作用，最终导致细胞周期的改变和细胞结构的变化，所有这些都有助于白血病的发展。这些影响的程度是由融合伴侣的功能域和伴随的体细胞突变的影响决定的。在这篇综述中，我们讨论了 NUP98 融合蛋白的复杂特征以及 NUP98 融合驱动的 AML 的潜在新颖治疗方法。© 2024 作者。约翰·威利 (John Wiley) 出版的 HemaSphere

Acute myeloid leukemia (AML) is an aggressive hematological malignancy with a heterogeneous molecular landscape. In the pediatric context, the NUP98 gene is a frequent target of chromosomal rearrangements that are linked to poor prognosis and unfavorable treatment outcomes in different AML subtypes. The translocations fuse NUP98 to a diverse array of partner genes, resulting in fusion proteins with novel functions. NUP98 fusion oncoproteins induce aberrant biomolecular condensation, abnormal gene expression programs, and re-wired protein interactions which ultimately cause alterations in the cell cycle and changes in cellular structures, all of which contribute to leukemia development. The extent of these effects is steered by the functional domains of the fusion partners and the influence of concomitant somatic mutations. In this review, we discuss the complex characteristics of NUP98 fusion proteins and potential novel therapeutic approaches for NUP98 fusion-driven AML.© 2024 The Author(s). HemaSphere published by John Wiley & Sons Ltd on behalf of European Hematology Association.