Ito Etsuro
Department of Community Medicine, Hirosaki University Graduate School of Medicine.
Rinsho Ketsueki. 2022;63(9):1115-1125. doi: 10.11406/rinketsu.63.1115.
Inherited bone marrow failure syndrome (IBMFS) is a heterogeneous group of genetic disorders characterized by bone marrow failure, congenital anomalies, and an increased risk of malignancy. The p53 tumor suppressor protein is a transcription factor activated in response to various cellular stresses and induces genes involved in apoptosis, cell cycle arrest, and DNA repair. Several lines of evidence suggest that p53 activation is central to the pathogenesis of IBMFS. We discovered germline TP53 activating mutations in IBMFS cases mimicking Diamond-Blackfan anemia using whole-exome sequencing. These cases were recognized as having a novel disorder, germline TP53 activation syndrome (bone marrow failure syndrome 5; OMIN). Recently, additional cases with the same TP53 mutations were reported, further clarifying the phenotype of this disease. This discovery confirms the hypothesis that p53 activation causes IBMFS. This review focuses on this novel IBMFS and discusses the link between p53 hyperactivation and IBMFS.
遗传性骨髓衰竭综合征（IBMFS）是一组异质性的遗传疾病，其特征为骨髓衰竭、先天性异常以及恶性肿瘤风险增加。p53肿瘤抑制蛋白是一种转录因子，在响应各种细胞应激时被激活，并诱导参与细胞凋亡、细胞周期停滞和DNA修复的基因。多条证据表明p53激活是IBMFS发病机制的核心。我们使用全外显子测序在模仿先天性纯红细胞再生障碍性贫血的IBMFS病例中发现了种系TP53激活突变。这些病例被认定为患有一种新型疾病，即种系TP53激活综合征（骨髓衰竭综合征5型；OMIM）。最近，又报道了其他具有相同TP53突变的病例，进一步明确了该疾病的表型。这一发现证实了p53激活导致IBMFS的假说。本综述聚焦于这种新型IBMFS，并讨论p53过度激活与IBMFS之间的联系。
