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以及治疗引起的婴儿、儿童和成人急性白血病有关。在这里，我们展示了从 2003 年至 2022 年间分析的 3401 名急性白血病患者获得的数据。确定了KMT2A基因内的基因组断点以及所涉及的易位伴侣基因 (TPG) 和KMT2A部分串联重复 (PTD)。包括文献中已发表的数据，目前已鉴定出107个框内KMT2A基因融合体。另外 16 例重排是框外融合，18 名患者没有与 5'- KMT2A融合的伴侣基因，两名患者有 5'- KMT2A缺失，一名ETV6::RUNX1患者在断点处有KMT2A插入。 7 个最常见的 TPG 和 PTD 占KMT2A所有重组的 90% 以上，其中 37 个重复出现，63 个迄今为止仅被识别一次。本研究对急性白血病患者的KMT2A重组组进行了全面分析。除了科学获取信息外，这些患者的基因组断点序列还被用来监测微小残留病（MRD）。因此，这项工作可以直接从实验室转移到患者的床边，满足提高患者生存率的临床需求。