Mutagenesis of GATA1 is an initiating event in Down syndrome leukemogenesis
Mutagenesis of GATA1 is an initiating event in Down syndrome leukemogenesis
复制标题
DOI：
10.1182/blood-2002-12-3904
复制
发表时间：
2003-06-01
期刊：
影响因子：
20.3
通讯作者：
Crispino, JD
中科院分区：
文献类型：
--
作者：
Mundschau, G;Gurbuxani, S;Crispino, JD
唐氏综合征（Down Syndrome，DS）患儿中有10%在出生时或出生后不久出现一过性骨髓增生性疾病（Temporary Myeloproliferative Disorder，TMD）。TMD的特征在于外周血和肝脏内大量的原始细胞，并且在大多数病例中显著地经历自发缓解。TMD可能是急性巨核细胞白血病（AMKL）的前兆，估计有30%的TMD患者在3年内发展为AMKL。我们最近报道，转录因子加塔1的突变与DS-AMKL相关。为了确定GATA 1突变的获得是否是急性白血病的晚期事件，我们分析了TMD患者DNA中的GATA 1。在这里，我们报告说，GATA 1突变的TMD原始细胞从每个婴儿检查。这些结果表明，加塔1可能在TMD的病因学中起关键作用，GATA 1的突变代表了DS髓系白血病发生的6个非常早期的事件。(C)2003年，美国血液学会。
As many as 10% of infants with Down syndrome (DS) present With transient myeloproliferative disorder (TMD) at or shortly after birth. TMD is characterized by an abundance of blasts Within the peripheral blood and liver, and notably undergoes spontaneous remission in the majority of cases. TMD may be a precursor to acute megakaryoblastic leukemia (AMKL), with an estimated 30% of TMD patients developing AMKL within 3 years. We recently reported, that mutations in the transcription factor GATA 1 are associated with DS-AMKL. To determine whether the acquisition of GATA1 mutations is a late event restricted to Acute leukemia, we analyzed GATA1 in DNA from TMD patients. Here we report that GATA1 is mutated in the TMD blasts from every infant examined. These results demonstrate that GATA 1 is likely to play a critical role in the etiology of TMD, and mutagenesis of GATA1 represents 6 very early event in DS myeloid leukemogenesis. (C) 2003 by The American Society of Hematology.