文章：

GATA1-相关白血病

GATA1-related leukaemias

原文发布日期：2008-04-01

DOI: 10.1038/nrc2348

类型: Review Article

开放获取: 否

要点：

1. GATA1 is an important transcription factor for the differentiation of the erythroid and megakaryocytic cell lineages through cooperative regulation of key molecules associated with proliferation, differentiation and apoptosis.
2. Mice that harbour a heterozygous Gata1-knockdown allele (Gata1.05) frequently develop erythroblastic leukaemias, showing that compromised Gata1 expression can be a causal factor in erythroid leukaemia.
3. Mutations in GATA1 that lead to the production of an amino-terminally truncated short form of the GATA1 protein contribute to cases of acute megakaryoblastic leukaemia and transient myeloproliferative disorder (TMD) that are seen in Down syndrome patients.
4. Mice expressing the short form of GATA1 protein exhibit an unusual accumulation of immature megakaryocytic progenitors during the embryonic and neonatal stages, and these hyperproliferative megakaryoblasts rapidly disappear during weaning, showing good agreement with the clinical course in TMD cases.
5. Leukaemias that are related to the quantitative and qualitative deficit of GATA1 function are collectively referred to as the GATA1-related leukaemias.
6. GATA1-related leukaemogenesis is a paradigm for multi-step disease and this process is likely to involve the participation of currently unidentified modifier genes.

要点翻译：

1. GATA1是一种重要的转录因子，通过协同调控与增殖、分化和凋亡相关的关键分子，促进红系和巨核细胞谱系的分化。
2. 携带杂合Gata1基因敲低等位基因（Gata1.05）的小鼠常发生成红细胞白血病，这表明Gata1表达受损可能是红系白血病的致病因素。
3. GATA1基因突变导致产生氨基末端截短的GATA1短蛋白形式，与唐氏综合征患者中出现的急性巨核细胞白血病和短暂性骨髓增殖性疾病病例相关。
4. 表达GATA1短蛋白形式的小鼠在胚胎期和新生儿期表现出未成熟巨核祖细胞的异常积聚，而这些过度增殖的原始巨核细胞在断奶期间迅速消失，与短暂性骨髓增殖性疾病的临床病程高度吻合。
5. 与GATA1功能定量和定性缺陷相关的白血病统称为GATA1相关白血病。
6. GATA1相关白血病的发生是多步骤疾病的范例，这一过程可能涉及目前尚未明确的修饰基因的参与。

英文摘要：

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.

摘要翻译： 

GATA1是一个典型的谱系限制性转录因子，对于红细胞和巨核细胞的正确分化、增殖和凋亡至关重要。GATA1的突变可以产生截短蛋白，这有助于患有唐氏综合征的婴儿发生短暂性骨髓增殖性疾病（TMD）和急性巨核细胞白血病（AMKL）。同样，将Gata1敲低至其野生型水平的5%会导致小鼠发生红细胞白血病的高发病率。GATA1相关白血病在人类和小鼠中都可能为多步骤白血病发生机制提供重要见解。目前正在进行努力，以产生反映TMD和AMKL的小鼠模型。

原文链接：

GATA1-related leukaemias