髓系恶性肿瘤中的 NUP98 融合:分子机制和治疗机会的最新进展

IF 7.6 2区 医学 Q1 HEMATOLOGY HemaSphere Pub Date : 2024-09-25 DOI:10.1002/hem3.70013
Milad Rasouli, Selina Troester, Florian Grebien, Bianca F. Goemans, C. Michel Zwaan, Olaf Heidenreich
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引用次数: 0

摘要

急性髓性白血病(AML)是一种侵袭性血液恶性肿瘤,具有异质性分子特征。在儿科,NUP98 基因是染色体重排的一个常见靶点,在不同的急性髓性白血病亚型中,染色体重排与预后不良和治疗效果不佳有关。这些易位将 NUP98 与一系列不同的伙伴基因融合,从而产生具有新功能的融合蛋白。NUP98 融合肿瘤蛋白会诱发异常的生物分子凝聚、异常的基因表达程序和重新配线的蛋白质相互作用,最终导致细胞周期的改变和细胞结构的变化,所有这些都会导致白血病的发展。这些影响的程度取决于融合伙伴的功能域以及伴随的体细胞突变的影响。在这篇综述中,我们将讨论 NUP98 融合蛋白的复杂特性以及 NUP98 融合驱动的急性髓细胞性白血病的潜在新型治疗方法。
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NUP98 oncofusions in myeloid malignancies: An update on molecular mechanisms and therapeutic opportunities

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.

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来源期刊
HemaSphere
HemaSphere Medicine-Hematology
CiteScore
6.10
自引率
4.50%
发文量
2776
审稿时长
7 weeks
期刊介绍: HemaSphere, as a publication, is dedicated to disseminating the outcomes of profoundly pertinent basic, translational, and clinical research endeavors within the field of hematology. The journal actively seeks robust studies that unveil novel discoveries with significant ramifications for hematology. In addition to original research, HemaSphere features review articles and guideline articles that furnish lucid synopses and discussions of emerging developments, along with recommendations for patient care. Positioned as the foremost resource in hematology, HemaSphere augments its offerings with specialized sections like HemaTopics and HemaPolicy. These segments engender insightful dialogues covering a spectrum of hematology-related topics, including digestible summaries of pivotal articles, updates on new therapies, deliberations on European policy matters, and other noteworthy news items within the field. Steering the course of HemaSphere are Editor in Chief Jan Cools and Deputy Editor in Chief Claire Harrison, alongside the guidance of an esteemed Editorial Board comprising international luminaries in both research and clinical realms, each representing diverse areas of hematologic expertise.
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