DCAL/Institute of Pharm. Biology, Goethe-University, Frankfurt/Main, Germany.
Instituto Nacional de Câncer (INCA), Rio de Janeiro, RJ, Brazil.
Leukemia. 2023 May;37(5):988-1005. doi: 10.1038/s41375-023-01877-1. Epub 2023 Apr 5.
Chromosomal rearrangements of the human KMT2A/MLL gene are associated with de novo as well as therapy-induced infant, pediatric, and adult acute leukemias. Here, we present the data obtained from 3401 acute leukemia patients that have been analyzed between 2003 and 2022. Genomic breakpoints within the KMT2A gene and the involved translocation partner genes (TPGs) and KMT2A-partial tandem duplications (PTDs) were determined. Including the published data from the literature, a total of 107 in-frame KMT2A gene fusions have been identified so far. Further 16 rearrangements were out-of-frame fusions, 18 patients had no partner gene fused to 5'-KMT2A, two patients had a 5'-KMT2A deletion, and one ETV6::RUNX1 patient had an KMT2A insertion at the breakpoint. The seven most frequent TPGs and PTDs account for more than 90% of all recombinations of the KMT2A, 37 occur recurrently and 63 were identified so far only once. This study provides a comprehensive analysis of the KMT2A recombinome in acute leukemia patients. Besides the scientific gain of information, genomic breakpoint sequences of these patients were used to monitor minimal residual disease (MRD). Thus, this work may be directly translated from the bench to the bedside of patients and meet the clinical needs to improve patient survival.
人类 KMT2A/MLL 基因的染色体重排与新发的以及治疗诱导的婴儿、儿科和成人急性白血病有关。在这里，我们展示了 2003 年至 2022 年期间分析的 3401 例急性白血病患者的数据。确定了 KMT2A 基因内的基因组断裂点以及涉及的易位伙伴基因（TPG）和 KMT2A-部分串联重复（PTD）。包括来自文献的已发表数据，迄今为止已鉴定出总共 107 个框内 KMT2A 基因融合。此外，还有 16 个是无框融合，18 个患者的 5'-KMT2A 没有与伙伴基因融合，两个患者的 5'-KMT2A 缺失，一个 ETV6::RUNX1 患者的 KMT2A 插入断点。七个最常见的 TPG 和 PTD 占 KMT2A 所有重组的 90%以上，37 个是反复发生的，到目前为止只有 63 个只出现过一次。这项研究提供了急性白血病患者 KMT2A 重组组的全面分析。除了获得科学信息之外，这些患者的基因组断裂点序列还用于监测微小残留病（MRD）。因此，这项工作可以直接从实验室转化为患者的床边，满足改善患者生存的临床需求。
