文章：

儿童白血病染色体易位的起源

Origins of chromosome translocations in childhood leukaemia

原文发布日期：2003-09-01

DOI: 10.1038/nrc1164

类型: Review Article

开放获取: 否

要点：

1. Different subtypes of leukaemia have distinctive chromosome translocations.
2. Translocations seem to arise at the level of haematopoietic stem cells, but their impact is cell-context dependent, resulting in different effects in different lineages.
3. Chromosome translocations are initiated by double-strand DNA breaks. The main repair mechanism underlying the resultant illegitimate recombination is probably non-homologous end-joining.
4. The products of balanced chromosome translocations are fusion genes, generating either a dysregulated partner gene or a chimeric fusion protein with new properties (either altered transcriptional regulation or constitutive kinase activity).
5. In childhood leukaemia, chromosome translocations arise mainly before birth during fetal haematopoiesis.
6. Chromosome translocations can initiate leukaemogenesis, but are usually not sufficient, with additional postnatal events being required.
7. The detailed understanding of chromosome translocations has implications for differential diagnosis, new therapies and molecular epidemiological studies that aim to uncover causality.

要点翻译：

1. 不同类型的白血病具有独特的染色体易位。
2. 染色体易位似乎发生在造血干细胞层面，但其影响具有细胞环境依赖性，在不同细胞系中产生不同效应。
3. 染色体易位由DNA双链断裂引发。其导致的异常重组主要修复机制可能为非 homologous 末端连接。
4. 平衡染色体易位的产物是融合基因，可能产生失调的伴侣基因或具有新特性的嵌合融合蛋白（改变转录调控或构成性激酶活性）。
5. 在儿童白血病中，染色体易位主要发生在出生前的胎儿造血期。
6. 染色体易位可启动白血病的发生，但通常并不充分，需要额外的出生后事件参与。
7. 对染色体易位的深入理解对鉴别诊断、新疗法以及旨在揭示病因的分子流行病学研究具有重要意义。

英文摘要：

Chromosome translocations are often early or initiating events in leukaemogenesis, occurring prenatally in most cases of childhood leukaemia. Although these genetic changes are necessary, they are usually not sufficient to cause leukaemia. How, when and where do translocations arise? And can these insights aid our understanding of the natural history, pathogenesis and causes of leukaemia?

摘要翻译： 

染色体易位通常是白血病发生过程中的早期或起始事件，在大多数儿童白血病病例中，这些易位在出生前就已发生。尽管这些遗传改变是必需的，但通常还不足以单独引发白血病。那么，这些易位是如何、何时以及在何处产生的？这些见解能否帮助我们更好地理解白血病的自然史、发病机制及其病因？

原文链接：

Origins of chromosome translocations in childhood leukaemia