Jude Craig D, Gaudet Justin J, Speck Nancy A, Ernst Patricia
Department of Genetics, Dartmouth Medical School, Hanover, New Hampshire 03755, USA.
Cell Cycle. 2008 Mar 1;7(5):586-91. doi: 10.4161/cc.7.5.5549. Epub 2008 Jan 1.
Chromosomal translocations that disrupt transcriptional regulators are frequently involved in the etiology of leukemia. To gain an understanding of the normal and pathologic roles of these transcriptional regulators, both gain- and loss-of-function mutations have been examined in the context of steady-state hematopoiesis. These studies have identified a remarkable number of genes whose loss-of-function phenotype includes a perturbation of hematopoietic stem cell (HSC) proliferation. As more of these models are generated and analyzed using commonly available tools, the regulatory pathways that control HSC quiescence and proliferation are becoming clearer. An emerging theme is that leukemia-associated transcriptional regulators coordinate the balance of proliferation and quiescence within the HSC pool by modulating the number and frequency of cells transiting the cell cycle. Uncoupling proliferation from differentiation by the aberrant generation of chimeric oncogenes that retain some, but not all of the attributes of the original transcription factor is likely to be an important step during leukemogenesis.
破坏转录调节因子的染色体易位常常与白血病的病因有关。为了了解这些转录调节因子的正常和病理作用，人们在稳态造血的背景下研究了功能获得和功能丧失突变。这些研究已经鉴定出大量基因，其功能丧失表型包括造血干细胞（HSC）增殖的扰动。随着越来越多的这些模型使用常用工具生成和分析，控制HSC静止和增殖的调节途径变得越来越清晰。一个新出现的主题是，白血病相关转录调节因子通过调节进入细胞周期的细胞数量和频率来协调HSC池内增殖和静止的平衡。通过异常产生保留原始转录因子部分但不是全部属性的嵌合癌基因，使增殖与分化解偶联可能是白血病发生过程中的一个重要步骤。
