Janssen J W, Ludwig W D, Sterry W, Bartram C R
Department of Pediatrics II, University of Ulm, Germany.
Leukemia. 1993 Aug;7(8):1204-10.
The TAL1 gene on chromosome 1 encodes a hematopoietic transcription factor. Disruption of TAL1 via chromosomal translocation or a site-specific deletion has been reported in up to 30% of T-cell acute lymphoblastic leukemias (T-ALL). Here we used a polymerase chain reaction (PCR) assay to identify the 90 kb SIL-TAL1 deletion in a group of 19 cutaneous T-cell lymphomas and a series of 142 T-ALL patients (76 children, 66 adults). While none of the T-cell lymphoma exhibited a SIL-TAL1 recombination, seven T-ALL cases showed a type d1 and two patients a type d2 deletion. Of pediatric T-ALL, 9% (7/76) and of adult patients only 3% (2/66) were characterized by this genomic lesion. The deletion correlated with commitment to the T-cell receptor (TCR) alpha beta lineage, but lacked association with a distinct maturation stage. Sequence analysis of SIL-TAL1 breakpoints revealed marked heterogeneity at the junctional region among the nine patients due to random deletion and insertion of N-region nucleotides or templated P-nucleotide addition mediated via illegitimate V(D)J recombinase action. Clonospecific oligomer probes in conjunction with PCR allowed the detection of minimal residual disease in one out of four patients monitored during complete hematologic remission.
位于1号染色体上的TAL1基因编码一种造血转录因子。据报道，在高达30%的T细胞急性淋巴细胞白血病（T-ALL）中，通过染色体易位或位点特异性缺失可导致TAL1基因破坏。在此，我们使用聚合酶链反应（PCR）分析，对一组19例皮肤T细胞淋巴瘤患者以及142例T-ALL患者（76例儿童，66例成人）进行检测，以确定是否存在90 kb的SIL-TAL1缺失。虽然所有皮肤T细胞淋巴瘤均未出现SIL-TAL1重组，但7例T-ALL病例出现了d1型缺失，2例患者出现了d2型缺失。在儿童T-ALL中，9%（7/76）、在成人患者中仅3%（2/66）存在这种基因组损伤。该缺失与T细胞受体（TCR）αβ谱系的定向分化相关，但与特定的成熟阶段无关。对SIL-TAL1断点的序列分析显示，由于N区核苷酸的随机缺失和插入，或通过非法V(D)J重组酶作用介导的模板化P核苷酸添加，9例患者的连接区存在明显的异质性。在完全血液学缓解期监测的4例患者中，有1例通过克隆特异性寡聚体探针结合PCR检测到微小残留病。
