Brown L, Cheng J T, Chen Q, Siciliano M J, Crist W, Buchanan G, Baer R
Department of Microbiology, University of Texas Southwestern Medical Center, Dallas.
EMBO J. 1990 Oct;9(10):3343-51. doi: 10.1002/j.1460-2075.1990.tb07535.x.
The tal-1 gene is altered as a consequence of the t(1;14) (p32;q11) chromosome translocation observed in 3% of patients with T cell acute lymphoblastic leukemia (T-ALL). tal-1 encodes a helix-loop-helix (HLH) domain, a DNA binding and dimerization motif found in a number of proteins involved in cell growth and differentiation. We now report that an additional 25% of T-ALL patients bear tal-1 gene rearrangements that are not detected by karyotype analysis. These rearrangements result from a precise 90 kb deletion (designated tald) that arises independently in different patients by site-specific DNA recombination. Since the deletion junctions resemble the coding joints of assembled immunoglobulin genes, tald rearrangements are likely to be mediated by aberrant activity of the immunoglobulin recombinase. Moreover, t(1;14)(p32;q11) translocations and tald rearrangements disrupt the coding potential of tal-1 in an equivalent manner, and thereby generate a common genetic lesion shared by a significant proportion of T-ALL patients.
在3%的T细胞急性淋巴细胞白血病（T-ALL）患者中观察到t(1;14)(p32;q11)染色体易位，tal-1基因因此发生改变。tal-1编码一个螺旋-环-螺旋（HLH）结构域，这是一种在许多参与细胞生长和分化的蛋白质中发现的DNA结合和二聚化基序。我们现在报告，另外25%的T-ALL患者存在tal-1基因重排，而核型分析未检测到这些重排。这些重排是由一个精确的90 kb缺失（称为tald）导致的，该缺失在不同患者中通过位点特异性DNA重组独立产生。由于缺失连接点类似于组装好的免疫球蛋白基因的编码接头，tald重排可能由免疫球蛋白重组酶的异常活性介导。此外，t(1;14)(p32;q11)易位和tald重排以相同的方式破坏tal-1的编码潜能，从而产生相当一部分T-ALL患者共有的常见遗传病变。
