Yamashita Takayuki
Laboratory of Molecular Genetics, Institute for Molecular and Cellular Regulation, Gunma University.
Rinsho Ketsueki. 2019;60(5):403-407. doi: 10.11406/rinketsu.60.403.
Fanconi anemia (FA) is a genetic disorder characterized by progressive bone marrow failure, increased susceptibility to leukemia and cancer, and genomic instabilities. Protein products encoded by 22 FA genes, identified till date, cooperate in a molecular pathway called the FA pathway to repair DNA interstrand cross-links induced by chemotherapeutic agents, such as mitomycin C and cisplatin. An accumulating number of studies have shown several new functional aspects of the FA pathway, particularly in the context of the pathogenesis of bone marrow failure. This review focuses on the following topics: (1) aldehydes as intrinsic interstrand cross-linkers; (2) cytokine-induced hematopoietic stress; (3) increased transforming growth factor-β signaling; (4) mitochondrial functions of FA proteins. These findings are expected to offer new therapeutic opportunities for bone marrow failure in FA.
范可尼贫血（FA）是一种遗传性疾病，其特征为进行性骨髓衰竭、对白血病和癌症的易感性增加以及基因组不稳定。迄今为止已鉴定出的22个FA基因所编码的蛋白质产物，在一条称为FA途径的分子途径中协同作用，以修复由化疗药物（如丝裂霉素C和顺铂）诱导的DNA链间交联。越来越多的研究显示了FA途径的几个新功能方面，特别是在骨髓衰竭发病机制的背景下。本综述聚焦于以下主题：（1）醛类作为内源性链间交联剂；（2）细胞因子诱导的造血应激；（3）转化生长因子-β信号传导增强；（4）FA蛋白的线粒体功能。这些发现有望为FA中的骨髓衰竭提供新的治疗机会。
