Prospective evaluation of prognostic impact of KIT mutations on acute myeloid leukemia with RUNX1-RUNX1T1 and CBFB-MYH11
Prospective evaluation of prognostic impact of KIT mutations on acute myeloid leukemia with RUNX1-RUNX1T1 and CBFB-MYH11
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DOI：
10.1182/bloodadvances.2019000709
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发表时间：
2020-01-14
期刊：
影响因子：
7.5
通讯作者：
Kiyoi, Hitoshi
中科院分区：
文献类型：
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作者：
Ishikawa, Yuichi;Kawashima, Naomi;Kiyoi, Hitoshi
KIT突变对核心结合因子急性髓系白血病（CBF-AML）预后的影响仍存在争议。我们登记了199名新诊断的新发CBF-AML患者，年龄在16至64岁之间，他们达到了完全缓解。他们接受了3个疗程的大剂量阿糖胞苷治疗，直到血液学复发才进一步治疗。分析KIT基因外显子8、10-11和17的突变。此外，我们分析了56个基因的突变，这些基因在骨髓恶性肿瘤中经常被发现，并评估了微小残留病（MRD）。主要终点是根据KIT突变的无复发生存期（RFS）。KIT突变患者的RFS劣于未突变患者（风险比，1.92; 95%置信区间，1.23-3.00; P=.003）。基于亚组分析，KIT突变对RUNX 1-RUNX 1 T1患者的预后有影响，但对CBFB-MYH 11患者无影响，仅外显子17突变对预后有显著影响。逐步选择的多变量考克斯回归分析显示，RUNX 1-RUNX 1 T1患者中KIT外显子17突变和髓外肿瘤的存在，以及CBFB-MYH 11患者中X或Y染色体缺失和NRAS突变是RFS的不良预后因素。在112例患者中评估了MRD，并且在CBFB-MYH 11患者中与较差的RFS相关，但在RUNX 1-RUNX 1 T1患者中与之无关。这些结果表明，有必要根据适当的预后因素分别评估AML与RUNX 1-RUNX 1 T1或CBFB-MYH 11。本研究在www.umin.ac.jp/ctr/注册为#UMIN000003434。
The prognostic impact of KIT mutation on core-binding factor acute myeloid leukemia (CBF-AML) remains controversial. We registered 199 newly diagnosed de novo CBF-AML patients, aged 16 to 64 years, who achieved complete remission. They received 3 courses of high-dose cytarabine therapy and no further treatment until hematological relapse. Mutations in exons 8, 10-11, and 17 of the KIT gene were analyzed. Furthermore, we analyzed mutations in 56 genes that are frequently identified in myeloid malignancies and evaluated minimal residual disease (MRD). The primary end point was relapse-free survival (RFS) according to KIT mutations. The RFS in KIT-mutated patients was inferior to that in unmutated patients (hazard ratio, 1.92; 95% confidence interval, 1.23-3.00; P=.003). Based on subgroup analysis, KIT mutations had a prognostic impact in patients with RUNX1-RUNX1T1, but not in those with CBFB-MYH11, and only exon 17 mutation had a significant prognostic impact. Multivariate Cox regression analysis with stepwise selection revealed that the KIT exon 17 mutation and the presence of extramedullary tumors in patients with RUNX1-RUNX1T1, and loss of chromosome X or Y and NRAS mutation in patients with CBFB-MYH11 were poor prognostic factors for RFS. MRD was evaluated in 112 patients, and it was associated with a poorer RFS in the patients with CBFB-MYH11, but not in those with RUNX1-RUNX1T1. These results suggested that it is necessary to separately evaluate AML with RUNX1-RUNX1T1 or CBFB-MYH11 according to appropriate prognostic factors. This study was registered at www.umin.ac.jp/ctr/ as #UMIN000003434.