Jonsson O G, Kitchens R L, Baer R J, Buchanan G R, Smith R G
Department of Pediatrics, University of Texas Southwestern Medical Center, Dallas 75235.
J Clin Invest. 1991 Jun;87(6):2029-35. doi: 10.1172/JCI115232.
Normal and aberrant immune receptor gene assembly each produce site-specific DNA rearrangements in leukemic lymphoblasts. In either case, these rearrangements provide useful clonal markers for the leukemias in question. In the t(1;14)(p34;q11) translocation associated with T cell acute lymphoblastic leukemia (T-ALL), the breakpoints on chromosome 1 interrupt the tal-1 gene. A site-specific deletion interrupts the same gene in an additional 26% of T-ALL. Thus, nearly one-third of these leukemias contain clustered rearrangements of the tal-1 locus. To test whether these rearrangements can serve as markers for residual disease, we monitored four patients with T-ALL; three of the leukemias contained a deleted (tald) and one a translocated (talt) tal-1 allele. These alleles were recognized by a sensitive amplification/hybridization assay. tald alleles were found in the blood of one patient during the 4th mo of treatment but not thereafter. Using a quantitative assay to measure the fraction of tald alleles in DNA extracts, we estimated that this month 4 sample contained 150 tald copies per 10(6) genome copies. The patient with t(1;14)(p34;q11) (talt) leukemia developed a positive assay during the 20th mo of treatment. By standard criteria, all four patients remain in complete remission 11-20 mo into treatment. We conclude that tal-1 rearrangements provide useful clonal markers for approximately 30% of T-ALLs.
正常和异常的免疫受体基因组装均在白血病淋巴母细胞中产生位点特异性DNA重排。在这两种情况下，这些重排都为相关白血病提供了有用的克隆标记。在与T细胞急性淋巴细胞白血病（T-ALL）相关的t(1;14)(p34;q11)易位中，1号染色体上的断点打断了tal-1基因。在另外26%的T-ALL中，一个位点特异性缺失也打断了同一个基因。因此，近三分之一的这些白血病含有tal-1基因座的成簇重排。为了测试这些重排是否可作为残留疾病的标记，我们监测了4例T-ALL患者；其中3例白血病含有缺失的（tald）tal-1等位基因，1例含有易位的（talt）tal-1等位基因。这些等位基因通过一种灵敏的扩增/杂交检测法得以识别。在治疗的第4个月时，在1例患者的血液中发现了tald等位基因，但之后未再发现。通过定量检测来测量DNA提取物中tald等位基因的比例，我们估计该第4个月的样本中每10(6)个基因组拷贝含有150个tald拷贝。患有t(1;14)(p34;q11)（talt）白血病的患者在治疗的第20个月时检测呈阳性。按照标准标准，所有4例患者在治疗11 - 20个月后仍处于完全缓解状态。我们得出结论，tal-1重排为大约30%的T-ALL提供了有用的克隆标记。
