Shimizu Ritsuko, Engel James Douglas, Yamamoto Masayuki
Center for Tsukuba Advanced Research Alliance, University of Tsukuba, 1-1-1 Tennoudai, Tsukuba 305-8577, Japan.
Nat Rev Cancer. 2008 Apr;8(4):279-87. doi: 10.1038/nrc2348.
GATA1 is a prototypical lineage-restricted transcription factor that is central to the correct differentiation, proliferation and apoptosis of erythroid and megakaryocytic cells. Mutations in GATA1 can generate a truncated protein, which contributes to the genesis of transient myeloproliferative disorder (TMD) and acute megakaryoblastic leukaemia (AMKL) in infants with Down syndrome. Similarly, Gata1 knockdown to 5% of its wild-type level causes high incidence of erythroid leukaemia in mice. The GATA1-related leukaemias in both human and mouse could provide important insights into the mechanism of multi-step leukaemogenesis. Efforts are afoot to produce mouse models that are reflective of TMD and AMKL.
GATA1是一种典型的谱系限制性转录因子，对红系和巨核细胞的正确分化、增殖和凋亡至关重要。GATA1突变可产生截短蛋白，这与唐氏综合征婴儿的短暂性骨髓增殖性疾病（TMD）和急性巨核细胞白血病（AMKL）的发生有关。同样，将Gata1敲低至其野生型水平的5%会导致小鼠红系白血病的高发病率。人类和小鼠中与GATA1相关的白血病可能为多步骤白血病发生机制提供重要见解。目前正在努力建立反映TMD和AMKL的小鼠模型。
