范可尼贫血蛋白与急性髓系白血病

范可尼贫血(FA)是一种罕见的常染色体隐性遗传性疾病,表现为进行性骨髓衰竭、先天性骨骼畸形和易患癌症等.FA患者细胞染色体自发不稳定,并对DNA交联剂如丝裂霉素C(MMC)高度敏感.因FA常发展成急性髓系白血病(AML),被认为是白血病前状态.目前已发现11种FA基因,通过共同的机制在维持细胞基因组稳定性中发挥作用.FANCF蛋白作为一种灵活的衔接蛋自在FA蛋白复合物正确组装形成过程中发挥着重要作用,它的形成使FANCD2蛋白单一泛素化,泛素化FANCD2蛋白导向染色质与乳腺癌抑制蛋白(BRCA1)相瓦作用,修复DNA损伤.FA基因缺陷将导致基因组不稳、染色体断裂的发生率增高,经过遗传损伤的积累最终导致AML及骨髓增生异常综合征(MDS)的发生.

Fanconi anemia protein and acute myeloid leukemia

Fanconi anemia (FA) is an rare autosomal recessive inherited disease which manifests progressive marrow failure, congenital bone malformation, high risk to cancers and so on. Chromatin of FA cells display auto-instability and high hypersensitivity to interstrand DNA cross-links such as mitomycin C. As normally FA develop into acute myeloid leukemia easily, it has been regarded as pre-leukemia state. Till now 11 FA genes have been found and play a role in sustaining stability of gene groups through the same mechanism. As an active connecting protein, FANCF protein play an important part in correct FA complex formation. Which makes FANCD2 single ubiquitin. Ubiquitin FANCD2 induces chromatin and BRCA1 interact, and repair injured DNA. FA gene defect makes gene group instable and increases the risk of chromatin collapse, which finally leads to acute myeloid leukemia and myelodysplastic syndrome.