In utero origin of t(8;21) AML1-ETO translocations in childhood acute myeloid leukemia
In utero origin of t(8;21) AML1-ETO translocations in childhood acute myeloid leukemia
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DOI：
10.1182/blood.v99.10.3801
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发表时间：
2002-05-15
期刊：
影响因子：
20.3
通讯作者：
Greaves, M
中科院分区：
文献类型：
--
作者：
Wiemels, JL;Xiao, ZJ;Greaves, M
最近的报道证实了一些患者的白血病易位和由此产生的融合基因的产前起源，包括婴儿的MLL-AF4易位和儿童的TEL-AML1易位。我们现在报告了儿童急性髓系白血病(AML)易位的产前起源的证据。在基因组水平上对10例有新生儿格思里血斑的诊断白血病患儿的t(8；21)AML1-ETO易位进行了测序。在格思里斑点检测到5个个体的克隆型基因组AML1-ETO序列，为这些病例的产前起源提供了明确的证据。其中两名患者在确诊时年龄超过10岁，表明出生后潜伏期延长。其中三名患者在完全临床缓解样本中对基因组融合序列的持久性进行了评估，结果发现呈阳性。这些数据表明，儿童AML中的t(8；21)可能发生在子宫中，可能是儿童AML的起始事件，并可能建立一个长期或稳定的亲代克隆，需要额外的次级基因改变才能引起白血病。(C)2002年，由美国血液病学会公布。
Recent reports have established the prenatal origin of leukemia translocations and resultant fusion genes in some patients, including MLL-AF4 translocations in infants and TEL-AML1 translocations in children. We now report evidence for the prenatal origin of a translocation in childhood acute myeloid leukemia (AML). The t(8;21) AML1-ETO translocations were sequenced at the genomic level in 10 diagnostic leukemia samples from children with available neonatal Guthrie blood spots. Clonotypic genomic AML1-ETO sequences were detected in the Guthrie spots for 5 individuals, providing unambiguous evidence of prenatal origin in these cases. Two of these patients were older than 10 years of age at diagnosis, indicative of a protracted postnatal latency. Three of the patients were assessed for the persistence of genomic fusion sequences in complete clinical remission samples and were found to be positive. These data indicate that t(8;21) in childhood AML can arise in utero, possibly as an initiating event in childhood AML, and may establish a long-lived or stable parental clone that requires additional secondary genetic alterations to cause leukemia. (C) 2002 by The American Society of Hematology.