PDF(Pubmed)
Abstract：
The translocation t(1;19)(q23;p13) with the resulting chimeric TCF3::PBX1 gene is the third most prevalent recurrent chromosomal translocation in acute lymphoblastic leukemia and accounts for 3-5% of cases. The molecular background of this translocation has been incompletely studied, especially in adult cases. We characterized the chromosomal breakpoints of 49 patients with TCF3::PBX1 and the corresponding reciprocal PBX1::TCF3 breakpoints in 15 cases at the molecular level, thus providing an extensive molecular overview of this translocation in a well-defined study patient population. Breakpoints were found to be remarkably clustered not only in TCF3 but also in PBX1. No association with DNA repeats or putative cryptic recombination signal sequence sites was observed. A simplified detection method for breakpoint identification was developed and the feasibility of patient-specific chromosomal break sites as molecular markers for detecting measurable residual disease (MRD) was explored. A highly sensitive generic real-time PCR for MRD assessment using these breakpoint sequences was established that could serve as a useful alternative to the classical method utilizing rearranged immune gene loci. This study provides the first extensive molecular data set on the chromosomal breakpoints of the t(1;19)/TCF3::PBX1 aberration in adult ALL. Based on the obtained data a generic MRD method was developed that has several theoretical advantages, including an on average higher sensitivity and a greater stability of the molecular marker in the course of disease.
摘要：
具有所得嵌合TCF3::PBX1基因的易位t(1;19)(q23;p13)是急性淋巴细胞白血病中第三普遍的复发性染色体易位,占病例的3-5%。这种易位的分子背景还没有得到充分的研究,尤其是在成人病例中。我们在分子水平上表征了49例TCF3::PBX1患者的染色体断点和15例相应的倒数PBX1::TCF3断点，因此，在明确定义的研究患者群体中提供了这种易位的广泛分子概述。发现断点不仅在TCF3中而且在PBX1中明显聚集。未观察到与DNA重复或推定的隐蔽重组信号序列位点的关联。开发了一种用于断点鉴定的简化检测方法，并探索了患者特异性染色体断裂位点作为检测可测量残留病（MRD）的分子标志物的可行性。建立了使用这些断点序列进行MRD评估的高度敏感的通用实时PCR，可作为利用重排免疫基因位点的经典方法的有用替代方法。这项研究提供了有关成人ALL中t（1;19）/TCF3：：PBX1畸变的染色体断点的第一个广泛的分子数据集。根据获得的数据，开发了一种具有几个理论优势的通用MRD方法，包括在疾病过程中分子标记的平均更高的灵敏度和更高的稳定性。
