Yoffe G, Schneider N, Van Dyk L, Yang C Y, Siciliano M, Buchanan G, Capra J D, Baer R
Department of Microbiology, University of Texas Southwestern Medical Center, Dallas 75235-9048.
Blood. 1989 Jul;74(1):374-9.
The translocation (11;14)(p13;q11) was observed in karyotypes of leukemic cells from a 3-year-old boy with T-cell acute lymphocytic leukemia (T-ALL). Since this translocation is a recurrent marker of T-ALL, we undertook to investigate its mode of formation and role in leukemogenesis. The cytogenetic breakpoint on chromosome 14 occurs in 14q11, the same band wherein lies the T-cell receptor alpha/delta chain gene; and Southern hybridization analysis of peripheral blood and bone marrow DNA uncovered a tumor-specific rearrangement in the D delta-J delta region of this locus. DNA encompassing the rearrangement was isolated by molecular cloning, and further analysis revealed it to be the t(11;14)(p13;q11) junction. Nucleotide sequence determination of the junction indicates that the 14q11 breakpoint occurs immediately adjacent to the D delta 2 gene segment. Hence, the translocation arose as an aberrant rearrangement between the downstream recombination signal of D delta 2 and a pseudo recombination signal adjacent to the chromosome 11 breakpoint. Finally, comparison of the breakpoint in band 11p13 with those of other translocations (11;14)(p13;q11) identified a breakpoint cluster region of approximately 1.2 kilobase-pairs (kb), alterations of which may promote the development of T-ALL.
在一名3岁患T细胞急性淋巴细胞白血病（T-ALL）男孩的白血病细胞染色体核型中观察到了（11；14）（p13；q11）易位。由于这种易位是T-ALL的一个常见标志物，我们着手研究其形成方式及其在白血病发生中的作用。14号染色体上的细胞遗传学断点位于14q11，即T细胞受体α/δ链基因所在的同一条带；对其外周血和骨髓DNA进行的Southern杂交分析发现，该位点的Dδ-Jδ区域存在肿瘤特异性重排。通过分子克隆分离出包含该重排的DNA，进一步分析显示其为t（11；14）（p13；q11）连接点。对该连接点的核苷酸序列测定表明，14q11断点紧邻Dδ2基因片段。因此，该易位是由Dδ2下游重组信号与11号染色体断点附近的一个假重组信号之间的异常重排产生的。最后，将11p13带中的断点与其他（11；14）（p13；q11）易位的断点进行比较，确定了一个约1.2千碱基对（kb）的断点簇区域，该区域的改变可能促进T-ALL的发展。
