Germline and Somatic Defects in DDX41 and its Impact on Myeloid Neoplasms.
Germline and Somatic Defects in DDX41 and its Impact on Myeloid Neoplasms.
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DOI：
10.1007/s11899-022-00667-3
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发表时间：
2022-10
影响因子：
2.9
通讯作者：
中科院分区：
文献类型：
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作者：
虽然DDX 41突变（m）是成人骨髓增生异常综合征（MDS）/急性髓性白血病（AML）中最常见的易感基因之一，但大多数患者并不总是存在MDS/AML家族史。在这篇综述中，我们将重点介绍DDX 41 m的流行病学数据，DDX 41在肿瘤发生中的作用，体细胞DDX 41 m的克隆进化机制，以及携带DDX 41 m的MDS/AML患者的临床表型和管理。DDX 41编码一种被认为对细胞生长和活力至关重要的DEAD盒解旋酶蛋白。携带DDX 41 m的患者中骨髓恶性肿瘤和其他癌症的高发病率表明，DDX 41的缺陷导致肿瘤抑制功能的丧失，可能与RNA剪接和加工途径中的活性有关。70%的DDX 41 m癌症病例仅与MDS/AML相关。超过65%的家族性病例具有杂合种系移码突变，其中p.D140Gfs*2是最常见的。在70%的病例中获得第二等位基因的体细胞DDX 41 m，导致血液恶性肿瘤。DDX 41 m骨髓肿瘤的典型特征是潜伏期长，表现为细胞遗传学正常且无任何其他分子标志物的高风险疾病。最近的报告表明，这些患者中的一个亚组具有惰性临床病程，并且与有利或中等风险AML相比具有更好的长期生存率。MDS/AML独特的临床/病理特征和良好的结局突出了对标准化分类和基因特异性指南的需求，这些指南可以帮助DDX 41 m患者的管理决策。
While DDX41 mutation (m) is one of the most prevalent predisposition genes in adult myelodysplastic syndrome (MDS)/acute myeloid leukemia (AML), most patients do not always present with a family history of MDS/AML. In this review, we will be highlighting epidemiological data on DDX41m, roles of DDX41 in oncogenesis, mechanisms of clonal evolution with somatic DDX41m, and clinical phenotypes and management of MDS/AML in patients harboring DDX41m. DDX41 encodes a DEAD-box helicase protein that is considered essential for cell growth and viability. High incidence of myeloid malignancies and other cancers in patients bearing DDX41m suggests that defects in DDX41 lead to loss of a tumor suppressor function, likely related to activities in RNA splicing and processing pathways. Seventy percent of cancer cases with DDX41m are associated with MDS/AML alone. More than 65% of familial cases harbor heterozygous germline frameshift mutations, of which p.D140Gfs*2 is the most common. A somatic DDX41m of the second allele is acquired in 70% of cases, leading to hematological malignancy. Myeloid neoplasms with DDX41m are typically characterized by long latency, high-risk disease at presentation with normal cytogenetics and without any additional molecular markers. Recent reports suggests that a subgroup of these patients have an indolent clinical course and have a better long-term survival compared to favorable or intermediate risk AML. Distinct clinical/pathologic features and favorable outcomes in MDS/AML highlight the need for standardized classification and gene specific guidelines that could assist in management decisions in patients with DDX41m.
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影响因子：
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作者：
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影响因子：
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