Mechanisms of leukemia translocations.
Mechanisms of leukemia translocations.
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DOI：
10.1097/moh.0b013e328302f711
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发表时间：
2008-07
影响因子：
3.2
通讯作者：
Hromas R
中科院分区：
文献类型：
--
作者：
Nickoloff JA;De Haro LP;Wray J;Hromas R
这篇综述强调了最近关于已知DNA修复机制的发现，它对染色体易位机制的影响以及它们在临床中与白血病的相关性。染色体易位调节白血病的行为。它们不仅能预测结果，还能定义治疗方法。关于白血病易位的产物有大量的知识，但对这些易位发生的机制知之甚少。考虑到在细胞周期的正常进程中发生的大量DNA双链断裂，特别是从V(D)J重组，停滞的复制分叉或失败的十烷化，令人惊讶的是，白血病易位并没有更频繁地发生。幸运的是，造血细胞有复杂的修复机制来抑制这种易位。当这些防御失败时，白血病变得更加常见，就像遗传的DNA修复缺陷一样。分析细胞和动物模型以及人类白血病中的易位序列，已经对白血病易位的机制产生了新的见解。来自动物模型的新数据表明，白血病易位的双重起源，其中必须同时存在DNA双链断裂修复缺陷和随后白血病发生的细胞周期阻滞失败。
This review highlights recent findings about the known DNA repair machinery, its impact on chromosomal translocation mechanisms and their relevance to leukemia in the clinic. Chromosomal translocations regulate the behavior of leukemia. They not only predict outcome but they define therapy. There is a great deal of knowledge on the products of leukemic translocations, yet little is known about the mechanism by which those translocations occur. Given the large number of DNA double-strand breaks that occur during normal progression through the cell cycle, especially from V(D)J recombination, stalled replication forks or failed decatenation, it is surprising that leukemogenic translocations do not occur more frequently. Fortunately, hematopoietic cells have sophisticated repair mechanisms to suppress such translocations. When these defenses fail leukemia becomes far more common, as seen in inherited deficiencies of DNA repair. Analyzing translocation sequences in cellular and animal models, and in human leukemias, has yielded new insights into the mechanisms of leukemogenic translocations. New data from animal models suggest a two hit origin of leukemic translocations, where there must be both a defect in DNA double-strand break repair and a subsequent failure of cell cycle arrest for leukemogenesis.