Fanconi anemia (FA) is an inherited disorder characterized by diverse congenital malformations, progressive pancytopenia, and predisposition to hematological malignancies and solid tumors. The role of the Fanconi anemia pathway in DNA repair mechanisms and genome instability is well studied. However, the consequences of inherited mutations in genes encoding the FA proteins and the acquired mutations due to impaired DNA repair complex in immune cells are far from understood. Patients with FA show bone marrow failure (BMF) and have a higher risk of developing myelodysplasia (MDS) or acute myeloid leukemia (AML) which are directly related to having chromosomal instability in hematopoietic stem cells and their subsequent progeny. However, immune dysregulation can also be seen in FA. As mature descendants of the common lymphoid progenitor line, NK cells taken from FA patients are dysfunctional in both NK cell-mediated cytotoxicity and cytokine production. The molecular bases for these defects are yet to be determined. However, recent studies have provided directions to define the cause and effect of inherited and acquired mutations in FA patients. Here, we summarize the recent studies in the hematopoietic dysfunction, focusing on the impairment in the development and functions of NK cells in FA patients, and discuss the possible mechanisms and future directions.

中文翻译：

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范可尼贫血患者的 NK 细胞发育和功能。

范可尼贫血 (FA) 是一种遗传性疾病，其特征是多种先天性畸形、进行性全血细胞减少以及易患血液系统恶性肿瘤和实体瘤。范可尼贫血通路在 DNA 修复机制和基因组不稳定性中的作用得到了很好的研究。然而，编码 FA 蛋白的基因的遗传突变以及免疫细胞中 DNA 修复复合物受损导致的获得性突变的后果尚不清楚。FA 患者表现出骨髓衰竭 (BMF)，并且发生骨髓增生异常 (MDS) 或急性髓系白血病 (AML) 的风险更高，这与造血干细胞及其后续后代的染色体不稳定直接相关。然而，在 FA 中也可以看到免疫失调。作为共同淋巴祖细胞系的成熟后代，取自 FA 患者的 NK 细胞在 NK 细胞介导的细胞毒性和细胞因子产生方面都存在功能障碍。这些缺陷的分子基础尚未确定。然而，最近的研究为确定 FA 患者遗传性和获得性突变的因果关系提供了方向。在此，我们总结了近期造血功能障碍的研究，重点关注FA患者NK细胞发育和功能受损，并讨论可能的机制和未来方向。