患有白血病的同卵双胞胎中TEL-AML1融合基因的胎儿起源。
Fetal origins of the TEL-AML1 fusion gene in identical twins with leukemia.
作者信息
Ford A M, Bennett C A, Price C M, Bruin M C, Van Wering E R, Greaves M
机构信息
Leukaemia Research Fund Centre, Institute of Cancer Research, Chester Beatty Laboratories, 237 Fulham Road, London SW3 6JB, United Kingdom.
出版信息
Proc Natl Acad Sci U S A. 1998 Apr 14;95(8):4584-8. doi: 10.1073/pnas.95.8.4584.
The TEL (ETV6)-AML1 (CBFA2) gene fusion is the most common reciprocal chromosomal rearrangement in childhood cancer occurring in approximately 25% of the most predominant subtype of leukemia- common acute lymphoblastic leukemia. The TEL-AML1 genomic sequence has been characterized in a pair of monozygotic twins diagnosed at ages 3 years, 6 months and 4 years, 10 months with common acute lymphoblastic leukemia. The twin leukemic DNA shared the same unique (or clonotypic) but nonconstitutive TEL-AML1 fusion sequence. The most plausible explanation for this finding is a single cell origin of the TEL-AML fusion in one fetus in utero, probably as a leukemia-initiating mutation, followed by intraplacental metastasis of clonal progeny to the other twin. Clonal identity is further supported by the finding that the leukemic cells in the two twins shared an identical rearranged IGH allele. These data have implications for the etiology and natural history of childhood leukemia.
TEL（ETV6）-AML1（CBFA2）基因融合是儿童癌症中最常见的相互染色体重排，约占最主要的白血病亚型——普通急性淋巴细胞白血病的25%。在一对分别于3岁6个月和4岁10个月时被诊断为普通急性淋巴细胞白血病的同卵双胞胎中，对TEL-AML1基因组序列进行了表征。这对双胞胎白血病DNA共享相同的独特（或克隆型）但非组成性的TEL-AML1融合序列。对此发现最合理的解释是，子宫内一个胎儿的TEL-AML融合起源于单个细胞，可能是作为白血病起始突变，随后克隆后代经胎盘转移至另一胎儿。两个双胞胎白血病细胞共享相同的重排IGH等位基因这一发现进一步支持了克隆同一性。这些数据对儿童白血病的病因学和自然史具有启示意义。
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