GATA1 mutations in transient leukemia and acute megakaryoblastic leukemia of Down syndrome
GATA1 mutations in transient leukemia and acute megakaryoblastic leukemia of Down syndrome
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DOI：
10.1182/blood-2003-01-0013
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发表时间：
2003-06-01
期刊：
影响因子：
20.3
通讯作者：
Zipursky, A
中科院分区：
文献类型：
--
作者：
Hitzler, JK;Cheung, J;Zipursky, A
先天性21三体综合征（唐氏综合征）的儿童患急性巨核细胞白血病（AMKL）的风险增加约500倍，AMKL是急性髓细胞白血病的一种。唐氏综合征新生儿特有的是短暂性白血病（TL），也称为短暂性骨髓增生综合征，在大多数情况下会自发缓解，但在大约20%的情况下，在以后的生活中会出现AMKL。最近的突变的基因编码的造血转录因子GATA1被证明是特异性的AMKL唐氏综合征。在这里，我们证明了GATA1突变存在于TL的原始细胞中，并且在TL和随后的AMKL期间从患者收集的连续样品中显示相同的GATA1突变。这些发现表明唐氏综合征AMKL的恶性转化模型，其中GATA1突变是早期事件，AMKL来自初始明显缓解后的潜伏TL克隆。(C)2003年，美国血液学会。
Children with constitutional trisomy 21 (Down syndrome) have an approximately 500-fold increased risk of developing acute megakaryoblastic leukemia (AMKL), a form of acute myelold leukemia. Unique to newborn infants with Down syndrome is a transient leukemia (TL), also referred to as transient myeloproliferative syndrome, that undergoes spontaneous remission in the majority of cases but in approximately 20% is followed by AMKL later in life. Recently mutations of the gene encoding the hematopoietic transcription factor GATA1 were shown to be specific for AMKL of Down syndrome. Here, we demonstrate that GATA1 mutations are present in blasts of TL and show the identical GATA1 mutation in sequential samples collected from a patient during TL and subsequent AMKL. These findings suggest a model of malignant transformation in Down syndrome AMKL in which GATA1 mutations are an early event and AMKL arises from latent TL clones following initial apparent remission. (C) 2003 by The American Society of Hematology.