Department of Hematology, Oncology and Tumor Immunology, CVK, Charité - Universitätsmedizin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany.
Department of Hematology, Oncology and Tumor Immunology, CBF, Charité - Universitätsmedizin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany.
Sci Rep. 2023 Sep 13;13(1):15167. doi: 10.1038/s41598-023-42294-9.
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.
t(1;19)(q23;p13)易位与由此产生的嵌合 TCF3::PBX1 基因是急性淋巴细胞白血病中第三大常见的复发性染色体易位，占病例的 3-5%。该易位的分子背景尚未完全研究，特别是在成人病例中。我们在分子水平上对 49 例 TCF3::PBX1 患者和 15 例相应的 PBX1::TCF3 易位断点进行了特征描述，从而为该易位在明确的研究患者群体中提供了广泛的分子概述。发现断点不仅在 TCF3 中，而且在 PBX1 中也明显聚集。未观察到与 DNA 重复序列或假定的隐蔽重组信号序列位点相关联。开发了一种用于断点识别的简化检测方法，并探讨了患者特异性染色体断裂点作为检测可测量残留疾病 (MRD) 的分子标志物的可行性。建立了一种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座的经典方法的有用替代方法。本研究提供了成人 ALL 中 t(1;19)/TCF3::PBX1 畸变的染色体断点的首个广泛的分子数据集。基于获得的数据，开发了一种通用的 MRD 方法，该方法具有几个理论优势，包括平均更高的敏感性和分子标志物在疾病过程中的更大稳定性。
