Matei Irina R, Guidos Cynthia J, Danska Jayne S
Program in Developmental Biology, The Hospital for Sick Children Research Institute, Toronto, Ontario, Canada.
Immunol Rev. 2006 Feb;209:142-58. doi: 10.1111/j.0105-2896.2006.00361.x.
The immune system is capable of recognizing and eliminating an enormous array of pathogens due to the extremely diverse antigen receptor repertoire of T and B lymphocytes. However, the development of lymphocytes bearing receptors with unique specificities requires the generation of programmed double strand breaks (DSBs) coupled with bursts of proliferation, rendering lymphocytes susceptible to mutations contributing to oncogenic transformation. Consequently, mechanisms responsible for monitoring global genomic integrity must be activated during lymphocyte development to limit the oncogenic potential of antigen receptor locus recombination. Mutations in ATM (ataxia-telangiectasia mutated), a kinase that coordinates DSB monitoring and the response to DNA damage, result in impaired T-cell development and predispose to T-cell leukemia. Here, we review recent evidence providing insight into the mechanisms by which ATM promotes normal lymphocyte development and protects from neoplastic transformation.
由于T淋巴细胞和B淋巴细胞具有极其多样的抗原受体库，免疫系统能够识别并清除大量病原体。然而，带有具有独特特异性受体的淋巴细胞的发育需要产生程序性双链断裂（DSB）并伴随着增殖爆发，这使得淋巴细胞易发生有助于致癌转化的突变。因此，在淋巴细胞发育过程中，负责监测整体基因组完整性的机制必须被激活，以限制抗原受体基因座重组的致癌潜力。共济失调毛细血管扩张症突变基因（ATM）是一种协调DSB监测和DNA损伤反应的激酶，其突变会导致T细胞发育受损，并易患T细胞白血病。在这里，我们综述了最近的证据，这些证据有助于深入了解ATM促进正常淋巴细胞发育并防止肿瘤转化的机制。
