Oncogenic transcription factors in the human acute leukemias
Oncogenic transcription factors in the human acute leukemias
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DOI：
10.1126/science.278.5340.1059
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发表时间：
1997-11-07
期刊：
影响因子：
56.9
通讯作者：
Look, AT
中科院分区：
文献类型：
--
作者：
Look, AT
人类急性白血病的染色体易位重排了多种转录因子基因的调控和编码区。由此产生的蛋白质产物可以干扰控制正常血细胞前体生长、分化和存活的调节级联反应。对这一解释的支持来自对小鼠的基因操作研究结果，以及致癌转录因子与已知调节原始生物胚胎发育的蛋白质的序列同源性，包括线虫秀丽线虫和果蝇黑腹果蝇。这些基因改变中的许多都具有重要的预后意义，可以指导治疗的选择。从易位致癌基因及其蛋白产物的研究中获得的见解应该会加速开发出高度特异的、因此毒性较低的白血病治疗方法。
Chromosomal translocations in the human acute leukemias rearrange the regulatory and coding regions of a variety of transcription factor genes. The resultant protein products can interfere with regulatory cascades that control the growth, differentiation, and survival of normal blood cell precursors. Support for this interpretation comes from the results of gene manipulation studies in mice, as well as the sequence homology of oncogenic transcription factors with proteins known to regulate embryonic development in primitive organisms, including the nematode Caenorhabditis elegans and the fruit fly Drosophila melanogaster. Many of these genetic alterations have important prognostic implications that can guide the selection of therapy. The insights gained from studies of translocation-generated oncogenes and their protein products should hasten the development of highly specific, and hence less toxic, forms of leukemia therapy.