Yano T, Pullman A, Andrade R, Uppenkamp M, de Villartay J P, Reaman G, Crush-Stanton S, Cohen D I, Raffeld M, Cossman J
Laboratory of Pathology, National Cancer Institute, National Institutes of Health, Bethesda, Md.
Br J Haematol. 1991 Sep;79(1):44-9. doi: 10.1111/j.1365-2141.1991.tb08005.x.
Despite their apparent commitment to the B lymphocytic lineage, human precursor B cell acute lymphoblastic leukaemias (ALL) frequently rearrange their T cell antigen receptor (TCR) alpha, beta and gamma chain genes. Since these three genes are active sites of rearrangement in precursor B cell neoplasms, it seemed that the recently discovered fourth TCR gene, delta, might be similarly rearranged. To investigate this possibility, a series of precursor B cell leukaemias was analysed for rearrangements at the delta chain gene locus, using probes of the variable, joining, and constant regions of the delta chain gene. The majority of precursor B cell ALLs in this series (25/32, 78%) showed rearrangement or deletion of one or more TCR delta genes. This contrasts sharply with a series of 16 mature B cell neoplasms (chronic lymphocytic leukaemia) in which no TCR delta gene rearrangements were detected. An unusual TCR delta rearrangement, rarely observed in normal or neoplastic T cells, was seen in the majority (14/18) of precursor B cell ALLs with TCR delta rearrangements. In contrast to the utilization ov V delta 1 in T cell ALL, detailed restriction mapping of precursor B ALL revealed an incomplete rearrangement without involvement of J delta segments. Direct genomic sequencing was performed on one example and demonstrated a nonproductive V delta 2-D delta 2-D delta 3 recombination in this precursor B ALL. We conclude that the TCR delta chain gene is an active locus in precursor B cell neoplasia, involves an unusual type of rearrangement and provides a clonal tumour marker for diagnosis of precursor B ALL.
尽管人类前体B细胞急性淋巴细胞白血病（ALL）明显倾向于B淋巴细胞谱系，但它们经常重排其T细胞抗原受体（TCR）的α、β和γ链基因。由于这三个基因是前体B细胞肿瘤中重排的活性位点，因此最近发现的第四个TCR基因δ似乎也可能发生类似的重排。为了研究这种可能性，使用δ链基因可变区、连接区和恒定区的探针，对一系列前体B细胞白血病进行了δ链基因位点重排分析。在该系列中的大多数前体B细胞ALL（25/32，78%）显示一个或多个TCRδ基因发生重排或缺失。这与一系列16例成熟B细胞肿瘤（慢性淋巴细胞白血病）形成鲜明对比，在这些肿瘤中未检测到TCRδ基因重排。在大多数（14/18）发生TCRδ重排的前体B细胞ALL中，观察到一种在正常或肿瘤性T细胞中很少见的异常TCRδ重排。与T细胞ALL中Vδ1的使用情况不同，前体B-ALL的详细限制性图谱显示重排不完全，未涉及Jδ片段。对一个例子进行了直接基因组测序，结果表明该前体B-ALL中存在非功能性的Vδ2-Dδ2-Dδ3重组。我们得出结论，TCRδ链基因是前体B细胞肿瘤形成中的一个活性位点，涉及一种异常的重排类型，并为前体B-ALL的诊断提供了一个克隆性肿瘤标志物。
