Protracted and variable latency of acute lymphoblastic leukemia after TEL-AML1 gene fusion in utero
Protracted and variable latency of acute lymphoblastic leukemia after TEL-AML1 gene fusion in utero
复制标题
DOI：
10.1182/blood.v94.3.1057.415k10_1057_1062
复制
发表时间：
1999-08-01
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;Ford, AM;Greaves, M
我们报告了一对患有一致急性淋巴细胞白血病（ALL）的同卵双胞胎。不同寻常的是，他们的诊断在 5 岁和 14 岁时相隔 9 年，双胞胎的白血病细胞都出现了 TEL-AML1 重排，这种重排通过长距离聚合酶链式反应 (PCR) 方法在 DNA 水平上进行表征。两种白血病的基因组融合序列是相同的，表明子宫内的一个胎儿具有单细胞起源。当双胞胎 1 被诊断时（5 岁），双胞胎 2 的骨髓血液学正常。然而，使用克隆型 TEL-AML1 引物对存档载玻片中的 DNA 进行回顾性检查表明，推定的白血病前期克隆在临床诊断前 9 年就已存在并传播。这些数据为儿童白血病的自然史提供了新的见解，并表明，由于白血病克隆在产前开始（很可能是由于 TEL-AML 融合本身），因此 ALL 的潜伏期可能变化极大且漫长。反过来，这可能反映了关键的次要事件的发生时间。 (C) 1999 年，美国血液学会。
We report a pair of identical twins with concordant acute lymphoblastic leukemia (ALL). Unusually, their diagnoses were spaced 9 years apart at ages 5 and 14, Leukemic cells in both twins had a TEL-AML1 rearrangement, which was characterized at the DNA level by an adaptation of a long distance polymerase chain reaction (PCR) method. The genomic fusion sequence was identical in the two leukemias, indicative of a single cell origin in one fetus, in utero. At the time twin 1 was diagnosed (aged 5 years), the bone marrow of twin 2 was hematologically normal. However, retrospective scrutiny of the DNA from an archived slide with clonotypic TEL-AML1 primers showed that the presumptive preleukemic clone was present and disseminated 9 years before a clinical diagnosis. These data provide novel insight into the natural history of childhood leukemia and suggest that consequent to a prenatal initiation of a leukemic clone, most probably by TEL-AML fusion itself, the latency of ALL can be both extremely variable and protracted. This, in turn, is likely to reflect the timing of critical secondary events. (C) 1999 by The American Society of Hematology.