TCF3::PBX1 基因重排所致的染色体易位 t(1;19)(q23;p13) 是急性淋巴细胞白血病中第三常见的复发性染色体易位，占到 3-5% 的病例。关于这种易位的分子背景研究尚不完整，特别是在成人病例中。我们对49名携带 TCF3::PBX1 基因重排的患者进行了染色体断点的分子特征分析，并在15例中进行了相应的 PBX1::TCF3 基因重排断点的分析，从而为一组定义明确的研究患者群体提供了对这种易位的广泛分子概览。我们发现，断点在 TCF3 和 PBX1 中的聚集现象非常显著。我们没有观察到与 DNA 重复序列或潜在的隐蔽重组信号序列位点的相关性。我们开发了一种简化的检测方法，用于检测断点位点，并探索了将患者特异性染色体断裂位点作为检测可测量残余疾病 (MRD) 的分子标记物的可行性。我们建立了一种高度敏感的通用实时 PCR 方法，用于利用这些断点序列评估 MRD，该方法可作为一种有用的替代方法，用于利用重排免疫基因座位进行 MRD 评估的经典方法。本研究提供了成人 ALL 中 t(1;19)/TCF3::PBX1 变异的第一份广泛的分子数据集。根据所获得的数据，我们开发了一种通用的 MRD 方法，具有几个理论上的优势，包括平均更高的敏感性和在疾病过程中更大的分子标记稳定性。© 2023 Springer Nature Limited.

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.© 2023. Springer Nature Limited.