Balanced rearrangements involving the KMT2A gene, located at 11q23, are among the most frequent chromosome aberrations in acute myeloid leukemia (AML). Because of numerous fusion partners, the mutational landscape and prognostic impact of specific 11q23/KMT2A rearrangements are not fully understood. We analyzed clinical features of 172 adults with AML and recurrent 11q23/KMT2A rearrangements, 141 of whom had outcome data available. We compared outcomes of these patients with outcomes of 1,097 patients without an 11q23/KMT2A rearrangement categorized according to the 2017 European LeukemiaNet (ELN) classification. Using targeted next-generation sequencing, we investigated the mutational status of 81 leukemia/cancer-associated genes in 96 patients with 11q23/KMT2A rearrangements with material for molecular studies available. Patients with 11q23/KMT2A rearrangements had a low number of additional gene mutations (median, 1; range 0 to 6), which involved the RAS pathway (KRAS, NRAS, and PTPN11) in 32% of patients. KRAS mutations occurred more often in patients with t(6;11)(q27;q23)/KMT2A-AFDN compared with patients with the other 11q23/KMT2A subsets. Specific gene mutations were too infrequent in patients with specific 11q23/KMT2A rearrangements to assess their associations with outcomes. We demonstrate that younger (age <60 y) patients with t(9;11)(p22;q23)/KMT2A-MLLT3 had better outcomes than patients with other 11q23/KMT2A rearrangements and those without 11q23/KMT2A rearrangements classified in the 2017 ELN intermediate-risk group. Conversely, outcomes of older patients (age ≥60 y) with t(9;11)(p22;q23) were poor and comparable to those of the ELN adverse-risk group patients. Our study shows that patients with an 11q23/KMT2A rearrangement have distinct mutational patterns and outcomes depending on the fusion partner.

涉及KMT2A基因的平衡重排位于11q23，是急性髓细胞性白血病（AML）中最常见的染色体畸变之一。由于存在众多融合伙伴，因此尚未完全了解特定11q23 / KMT2A重排的突变情况和预后影响。我们分析了172例AML和复发性11q23 / KMT2A重排的成年人的临床特征，其中141例具有可用的结局数据。我们比较了这些患者的结果和1,097例没有11q23 / KMT2A的患者的结果重排根据2017年欧洲LeukemiaNet（ELN）分类进行了分类。使用靶向的下一代测序，我们调查了96名11q23 / KMT2A重排患者中81个与癌症/癌症相关的基因的突变状态，并提供了可用于分子研究的材料。患有11q23 / KMT2A重排的患者中，有32％的患者具有较少的其他基因突变（中位数为1；范围为0至6），其中涉及RAS途径（KRAS，NRAS和PTPN11）。与其他11q23 / KMT2A患者相比，t（6; 11）（q27; q23）/ KMT2A - AFDN患者中KRAS突变发生率更高子集。具有特定11q23 / KMT2A重排的患者中，特定基因突变太少了，无法评估其与预后的关系。我们证明，t（9; 11）（p22; q23）/ KMT2A - MLLT3的年轻（年龄<60岁）患者比其他11q23 / KMT2A重排和没有11q23 / KMT2A重排的患者在2017年ELN中有更好的结局中危人群。相反，t（9; 11）（p22; q23）的老年患者（年龄≥60岁）的预后较差，与ELN不良风险组患者的预后相当。我们的研究表明，患有11q23 / KMT2A的患者 根据融合伴侣，重排具有独特的突变模式和结果。