Aplan P D, Raimondi S C, Kirsch I R
Navy Medical Branch, National Cancer Institute, Bethesda, Maryland 20889.
J Exp Med. 1992 Nov 1;176(5):1303-10. doi: 10.1084/jem.176.5.1303.
SCL gene disruptions are the most common chromosomal abnormality associated with the development of T cell acute lymphoblastic leukemia (ALL). Such disruptions can be the result of t(1;14) and t(1;7) translocations, as well as a cytogenetically undetectable interstitial deletion of chromosome 1. We present here a case of T cell ALL with a t(1;3)(p34;p21) translocation that also disrupts the SCL locus and leads to dysregulated SCL gene expression. This translocation, similar to previously reported SCL gene disruptions, appears to have been mediated, at least in part, by the V(D)J recombinase complex, since cryptic heptamer recognition sequences, as well as nontemplated N region nucleotide addition, are present at the breakpoints. The t(1;3) also disrupts a region on chromosome 3 characterized by alternating purine and pyrimidine residues, which can form a Z-DNA structure, reported to be prone to recombination events. A previously undescribed, evolutionarily conserved transcript unit is detected within 8 kb of the breakpoint on chromosome 3. This report extends the spectrum of recognized SCL translocations associated with T cell ALL, and underscores the contention that dysregulated SCL expression may be a causal event in T cell ALL.
SCL基因破坏是与T细胞急性淋巴细胞白血病（ALL）发生相关的最常见染色体异常。此类破坏可能是t(1;14)和t(1;7)易位的结果，也可能是1号染色体上细胞遗传学无法检测到的间质缺失。我们在此报告一例T细胞ALL病例，其存在t(1;3)(p34;p21)易位，该易位同样破坏了SCL基因座并导致SCL基因表达失调。与先前报道的SCL基因破坏相似，这种易位似乎至少部分是由V(D)J重组酶复合物介导的，因为在断点处存在隐蔽的七聚体识别序列以及非模板化的N区核苷酸添加。t(1;3)还破坏了3号染色体上一个以嘌呤和嘧啶残基交替为特征的区域，该区域可形成Z-DNA结构，据报道这种结构易于发生重组事件。在3号染色体断点的8 kb范围内检测到一个先前未描述的、进化上保守的转录单位。本报告扩展了与T细胞ALL相关的已识别SCL易位谱，并强调了SCL表达失调可能是T细胞ALL病因这一观点。
