D816 mutation of the KIT gene in core binding factor acute myeloid leukemia is associated with poorer prognosis than other KIT gene mutations
D816 mutation of the KIT gene in core binding factor acute myeloid leukemia is associated with poorer prognosis than other KIT gene mutations
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DOI：
10.1007/s00277-017-3074-y
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发表时间：
2017-10-01
影响因子：
3.5
通讯作者：
Inokuchi, Koiti
中科院分区：
文献类型：
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作者：
Yui, Shunsuke;Kurosawa, Saiko;Inokuchi, Koiti
KIT突变对核心结合因子急性髓系白血病（CBF-AML）的临床影响尚不清楚。在本研究中，我们分析了每种KIT突变（D816、N822K和其他突变）在日本CBF-AML患者中的预后意义。我们回顾性分析了136例进入完全缓解（CR）的CBF-AML病例。在61例（45%）CBF-AML患者中发现KIT突变。D816、N822K、D816和N822K等KIT基因突变分别为29例（21%）、20例（15%）、7例（5%）和5例（4%）。D816、D816和N822K突变患者的无复发生存率（RFS）和总生存率（OS）显著低于其他KIT突变或无KIT突变患者（RFS: p < 0.001, OS: p < 0.001）。此外，对染色体异常t(8;21)（q22;q22）和inv(16)（p13.1q22）、t(16;16)（p13.1;q22）的分层分析显示，D816突变与预后明显较差相关。在进一步的RFS和OS的多变量分析中，发现D816突变是显著较差预后的独立危险因素。在目前的研究中，我们能够确定，在所有KIT突变中，D816突变单独是一个不利的预后因素。
The clinical impact of KIT mutations in core binding factor acute myeloid leukemia (CBF-AML) is still unclear. In the present study, we analyzed the prognostic significance of each KIT mutation (D816, N822K, and other mutations) in Japanese patients with CBF-AML. We retrospectively analyzed 136 cases of CBF-AML that had gone into complete remission (CR). KIT mutations were found in 61 (45%) of the patients with CBF-AML. D816, N822K, D816 and N822K, and other mutations of the KIT gene were detected in 29 cases (21%), 20 cases (15%), 7 cases (5%), and 5 cases (4%), respectively. The rate of relapse-free survival (RFS) and overall survival (OS) in patients with D816 and with both D816 and N822K mutations was significantly lower than in patients with other or with no KIT mutations (RFS: p < 0.001, OS: p < 0.001). Moreover, stratified analysis of the chromosomal abnormalities t(8;21)(q22;q22) and inv(16)(p13.1q22), t(16;16)(p13.1;q22) showed that D816 mutation was associated with a significantly worse prognosis. In a further multivariate analysis of RFS and OS, D816 mutation was found to be an independent risk factor for significantly poorer prognosis. In the present study, we were able to establish that, of all KIT mutations, D816 mutation alone is an unfavorable prognostic factor.