Dakic Aleksandar, Wu Li, Nutt Stephen L
The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria 3050, Australia.
Trends Immunol. 2007 Mar;28(3):108-14. doi: 10.1016/j.it.2007.01.006. Epub 2007 Jan 30.
The transcription factor PU.1 is an essential regulator of haemopoiesis and a suppressor of myeloid leukaemia. PU.1 displays a complex expression pattern characterized by high expression in myeloid cells and low amounts in lymphoid cells. Based on this transcriptional profile, and the analysis of cell lines and mice expressing altered levels of PU.1, a model has been proposed where the concentration of PU.1 determines cell fate, whereas the graded reduction, but not absence, of PU.1 facilitates leukaemogenesis. The recent reports of mouse strains that enable the accurate determination of PU.1 expression and the conditional inactivation of PU.1 in adult haemopoiesis have led us to re-examine our understanding of the complex functions of PU.1. Here, we will discuss the data that, we believe, argue against the dosage-sensitive model of PU.1-mediated lineage commitment and leukaemogenesis.
转录因子PU.1是造血过程中的关键调节因子，也是髓系白血病的抑制因子。PU.1呈现出复杂的表达模式，其特征是在髓系细胞中高表达，而在淋巴细胞中表达量较低。基于这种转录谱，以及对表达水平改变的PU.1的细胞系和小鼠的分析，有人提出了一种模型，即PU.1的浓度决定细胞命运，而PU.1的逐步降低（而非缺失）会促进白血病发生。最近有关于能够精确测定PU.1表达以及在成年造血过程中对PU.1进行条件性失活的小鼠品系的报道，这促使我们重新审视对PU.1复杂功能的理解。在此，我们将讨论我们认为与PU.1介导的谱系定向和白血病发生的剂量敏感模型相悖的数据。
