Breit T M, Mol E J, Wolvers-Tettero I L, Ludwig W D, van Wering E R, van Dongen J J
Department of Immunology, University Hospital Dijkzigt/Erasmus University, Rotterdam, The Netherlands.
J Exp Med. 1993 Apr 1;177(4):965-77. doi: 10.1084/jem.177.4.965.
Site-specific deletions in the tal-1 gene are reported to occur in 12-26% of T cell acute lymphoblastic leukemias (T-ALL). So far two main types of tal-1 deletions have been described. Upon analysis of 134 T-ALL we have found two new types of tal-1 deletions. These four types of deletions juxtapose the 5' part of the tal-1 gene to the sil gene promoter, thereby deleting all coding sil exons but leaving the coding tal-1 exons undamaged. The recombination signal sequences (RSS) and fusion regions of the tal-1 deletion breakpoints strongly resemble the RSS and junctional regions of immunoglobulin/T cell receptor (TCR) gene rearrangements, which implies that they are probably caused by the same V(D)J recombinase complex. Analysis of the 134 T-ALL suggested that the occurrence of tal-1 deletions is associated with the CD3 phenotype, because no tal-1 deletions were found in 25 TCR-gamma/delta + T-ALL, whereas 8 of the 69 CD3- T-ALL and 11 of the 40 TCR-alpha/beta + T-ALL contained such a deletion. Careful examination of all TCR genes revealed that tal-1 deletions exclusively occurred in CD3- or CD3+ T-ALL of the alpha/beta lineage with a frequency of 18% in T-ALL with one deleted TCR-delta allele, and a frequency of 34% in T-ALL with TCR-delta gene deletions on both alleles. Therefore, we conclude that alpha/beta lineage commitment of the T-ALL and especially the extent of TCR-delta gene deletions determines the chance of a tal-1 deletion. This suggests that tal-1 deletions are mediated via the same deletion mechanism as TCR-delta gene deletions.
据报道，在12%至26%的T细胞急性淋巴细胞白血病（T-ALL）中会出现tal-1基因的位点特异性缺失。到目前为止，已经描述了两种主要类型的tal-1缺失。在对134例T-ALL进行分析后，我们发现了两种新类型的tal-1缺失。这四种类型的缺失将tal-1基因的5'部分与sil基因启动子并列，从而删除了所有编码sil的外显子，但tal-1的编码外显子未受损。tal-1缺失断点的重组信号序列（RSS）和融合区域与免疫球蛋白/T细胞受体（TCR）基因重排的RSS和连接区域非常相似，这意味着它们可能是由相同的V(D)J重组酶复合物引起的。对134例T-ALL的分析表明，tal-1缺失的发生与CD3表型相关，因为在25例TCR-γ/δ + T-ALL中未发现tal-1缺失，而在69例CD3- T-ALL中的8例以及40例TCR-α/β + T-ALL中的11例含有这种缺失。对所有TCR基因的仔细检查发现，tal-1缺失仅发生在α/β谱系的CD3-或CD3+ T-ALL中，在一个TCR-δ等位基因缺失的T-ALL中频率为18%，在两个等位基因均有TCR-δ基因缺失的T-ALL中频率为34%。因此，我们得出结论，T-ALL的α/β谱系定向，尤其是TCR-δ基因缺失的程度决定了tal-1缺失的可能性。这表明tal-1缺失是通过与TCR-δ基因缺失相同的缺失机制介导的。
