Bash R O, Hall S, Timmons C F, Crist W M, Amylon M, Smith R G, Baer R
Department of Pediatrics, University of Texas Southwestern Medical Center, Dallas 75235-9048, USA.
Blood. 1995 Jul 15;86(2):666-76.
Almost 25% of patients with T-cell acute lymphoblastic leukemia (T-ALL) have tumor-specific rearrangements of the TAL1 gene. Although TAL1 expression has not been observed in normal lymphocytes, TAL1 gene products are readily detected in leukemic cells that harbor a rearranged TAL1 allele. Hence, it has been proposed that ectopic expression of TAL1 promotes the development of T-ALL. In this report, we show that TAL1 is expressed in the leukemic cells of most patients with T-ALL, including many that do not display an apparent TAL1 gene alteration. A polymorphic dinucleotide repeat in the transcribed sequences of TAL1 was used to determine the allele specificity of TAL1 transcription in primary T-ALL cells. Monoallelic expression of TAL1 was observed in the leukemic cells of all patients (8 of 8) bearing a TAL1 gene rearrangement. In the leukemic cells of patients without detectable TAL1 rearrangements, TAL1 transcription occurred in either a monoallelic (3 of 7 patients) or a biallelic (4 of 7 patients) fashion. Thus, TAL1 activation in these patients may result from subtle alterations in cis-acting regulatory sequences (affecting expression of a single TAL1 allele) or changes in trans-acting factors that control TAL1 transcription (affecting expression of both TAL1 alleles).
近25%的T细胞急性淋巴细胞白血病（T-ALL）患者存在TAL1基因的肿瘤特异性重排。虽然在正常淋巴细胞中未观察到TAL1表达，但在携带重排TAL1等位基因的白血病细胞中很容易检测到TAL1基因产物。因此，有人提出TAL1的异位表达促进了T-ALL的发展。在本报告中，我们表明TAL1在大多数T-ALL患者的白血病细胞中表达，包括许多未显示明显TAL1基因改变的患者。TAL1转录序列中的一个多态性二核苷酸重复序列被用于确定原发性T-ALL细胞中TAL1转录的等位基因特异性。在所有携带TAL1基因重排的患者（8例中的8例）的白血病细胞中均观察到TAL1的单等位基因表达。在未检测到TAL1重排的患者的白血病细胞中，TAL1转录以单等位基因（7例中的3例）或双等位基因（7例中的4例）方式发生。因此，这些患者中TAL1的激活可能是由于顺式作用调节序列的细微改变（影响单个TAL1等位基因的表达）或控制TAL1转录的反式作用因子的变化（影响两个TAL1等位基因的表达）所致。
