The Ohio State University Comprehensive Cancer Center, Columbus, OH 43210;
The Ohio State University Comprehensive Cancer Center, Columbus, OH 43210.
Proc Natl Acad Sci U S A. 2020 Oct 20;117(42):26340-26346. doi: 10.1073/pnas.2014732117. Epub 2020 Oct 5.
Balanced rearrangements involving the 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/ rearrangements are not fully understood. We analyzed clinical features of 172 adults with AML and recurrent 11q23/ rearrangements, 141 of whom had outcome data available. We compared outcomes of these patients with outcomes of 1,097 patients without an 11q23/ 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/ rearrangements with material for molecular studies available. Patients with 11q23/ rearrangements had a low number of additional gene mutations (median, 1; range 0 to 6), which involved the RAS pathway (, , and ) in 32% of patients. mutations occurred more often in patients with t(6;11)(q27;q23)/- compared with patients with the other 11q23/ subsets. Specific gene mutations were too infrequent in patients with specific 11q23/ rearrangements to assess their associations with outcomes. We demonstrate that younger (age <60 y) patients with t(9;11)(p22;q23)/- had better outcomes than patients with other 11q23/ rearrangements and those without 11q23/ 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/ rearrangement have distinct mutational patterns and outcomes depending on the fusion partner.
涉及基因的平衡重排，该基因位于 11q23，是急性髓细胞白血病 (AML) 中最常见的染色体异常之一。由于有许多融合伙伴，特定 11q23/重排的突变景观和预后影响尚未完全了解。我们分析了 172 名成人 AML 患者和复发性 11q23/重排患者的临床特征，其中 141 名患者有可用的结局数据。我们将这些患者的结局与根据 2017 年欧洲白血病网 (ELN) 分类的 1097 名无 11q23/重排的患者的结局进行了比较。使用靶向下一代测序，我们研究了 96 名 11q23/重排患者中 81 个白血病/癌症相关基因的突变状态，这些患者有用于分子研究的材料。有 11q23/重排的患者有较少的额外基因突变（中位数为 1；范围 0 至 6），其中 32%的患者涉及 RAS 途径（NRAS、KRAS 和 BRAF）。与其他 11q23/亚组相比，在 t(6;11)(q27;q23)/-的患者中更常发生 突变。由于特定 11q23/重排患者的特定基因突变过于罕见，无法评估其与结局的关联。我们证明，年龄小于 60 岁的 t(9;11)(p22;q23)/-患者的结局优于其他 11q23/重排患者和 2017 年 ELN 中危组中无 11q23/重排的患者。相反，年龄大于 60 岁的 t(9;11)(p22;q23)患者的结局较差，与 ELN 不良风险组患者的结局相当。我们的研究表明，根据融合伙伴的不同，携带 11q23/重排的患者具有不同的突变模式和结局。
