Clinical and mechanistic insights into the roles of DDX41 in haematological malignancies.
Clinical and mechanistic insights into the roles of DDX41 in haematological malignancies.
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DOI：
10.1002/1873-3468.14487
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发表时间：
2022-11
期刊：
影响因子：
3.5
通讯作者：
Bowman, Teresa, V
中科院分区：
文献类型：
--
作者：
Weinreb, Joshua T.;Bowman, Teresa, V
关键词：
DEAD 盒解旋酶41（DDX41）是DExD/H 盒解旋酶家族的成员，具有多种细胞功能。值得注意的是，DDX41基因的种系和体细胞突变普遍存在于髓系恶性肿瘤中。在此，我们对DDX41相关的临床、转化医学及基础科学研究结果进行了全面且具分析性的综述。我们首先阐述了在骨髓增生异常综合征患者中DDX41突变的初步特征、相关临床特点以及当前的治疗方式。接着，我们介绍了DDX41已知的细胞功能，从其在果蝇中作为神经调节因子被发现，到近期所描述的在炎症信号传导、R环代谢和核仁小分子RNA（snoRNA）加工中的作用。最后，我们总结了已明确的DDX41基本功能，这些功能一旦受到干扰，可能会导致血液系统肿瘤的潜在病理变化。
DEAD 盒解旋酶41（DDX41）基因在遗传性和散发性血液系统恶性肿瘤中经常发生突变。种系和体细胞突变会降低DDX41的水平或活性，这表明抑制DDX41会促进血液系统恶性肿瘤的发生。DDX41在R环调控、环鸟苷酸 - 腺苷酸合成酶（cGAS）炎症调节、前体信使核糖核酸（pre - mRNA）剪接以及snoRNA/核糖体核糖核酸（rRNA）加工方面的缺陷，也与造血功能障碍的起始有关。
DEAD-box Helicase 41 (DDX41) is a member of the DExD/H-box helicase family that has a variety of cellular functions. Of note, germline and somatic mutations in the DDX41 gene are prevalently found in myeloid malignancies. Here, we present a comprehensive and analytic review covering relevant clinical, translational, and basic science findings on DDX41. We first describe the initial characterization of DDX41 mutations in patients affected by myelodysplastic syndromes, their associated clinical characteristics, and current treatment modalities. We then cover the known cellular functions of DDX41, spanning from its discovery in Drosophila as a neuroregulator through its more recently described roles in inflammatory signaling, R-loop metabolism, and snoRNA processing. We end with a summary of the identified basic functions of DDX41 that when perturbed may contribute to the underlying pathology of hematologic neoplasms. The DEAD-box Helicase 41 (DDX41) gene is commonly mutated in inherited and sporadic hematologic malignancies. Germline and somatic mutations diminish DDX41 levels or activity, suggesting that DDX41 inhibition promotes hematologic malignancy. Deficits in R-loop regulation, cGAS inflammatory modulation, pre-mRNA splicing, and snoRNA/rRNA processing by DDX41 have also been implicated in the initiation of hematopoietic dysfunction.
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