Importance of c-kit mutation detection method sensitivity in prognostic analyses of t(8;21)(q22;q22) acute myeloid leukemia
Importance of c-kit mutation detection method sensitivity in prognostic analyses of t(8;21)(q22;q22) acute myeloid leukemia
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DOI：
10.1038/leu.2011.104
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发表时间：
2011-09
期刊：
影响因子：
11.4
通讯作者：
S. Wakita;H. Yamaguchi;Koichi Miyake;Y. Mitamura;F. Kosaka;Kazuo Dan;K. Inokuchi
中科院分区：
文献类型：
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作者：
S. Wakita;H. Yamaguchi;Koichi Miyake;Y. Mitamura;F. Kosaka;Kazuo Dan;K. Inokuchi
近年来，c-kit基因突变被认为是急性髓系白血病t(8；21)(q22；q22)易位(t(8；21)AML)的一个新的不良预后因素。然而，它的临床意义仍不清楚。在这项研究中，我们建立了一种高灵敏度的突变检测方法，称为突变偏向聚合酶链式反应(MB-PCR)，并研究了c-kit突变与预后的关系。对26例t(8；21)AML患者采用直接测序(DS)和MB-PCR法进行c-kit突变分析，后者初诊时c-kit基因突变的检出率(DS 5/26(19.2%)vsMB-PCR12/26(46.2%))。有趣的是，在这三个病例中，只有在DS复发时才观察到c-kit突变，而c-kit突变是在最初表现时使用MB-PCR检测到的。这一结果表明，一个带有c-kit突变的微小白血病克隆对治疗具有抵抗力，并与复发有关。在单因素分析中，使用DS的c-kit突变不是不良预后因素(P=0.355)，但在使用MB-PCR时是一个因素(P=0.014)。多因素分析显示，MB-PCRc-kit基因突变也是一个独立的不良预后因素(P=0.006)。结论：c-kit基因突变检测方法的敏感性对t(8；21)AML的预后判断有重要意义。
Recently, c-kit mutations have been reported as a novel adverse prognostic factor of acute myeloid leukemia with t (8; 21)(q22; q22) translocation (t (8; 21) AML). However, much remains unclear about its clinical significance. In this study, we developed a highly sensitive mutation detection method known as mutation-biased PCR (MB-PCR) and investigated the relationship between c-kit mutations and prognosis. When c-kit mutations were analyzed for 26 cases of t (8; 21) AML using the direct sequence (DS) and MB-PCR, the latter had a much higher detection rate of c-kit mutations at initial presentation (DS 5/26 (19.2%) vs MB-PCR 12/26 (46.2%)). Interestingly for the three cases, in which c-kit mutations were observed only at relapse with the DS, c-kit mutations were detected at initial presentation using the MB-PCR. This result suggests that a minor leukemia clone with c-kit mutations have resistance to treatment and are involved in relapse. In univariate analyses, the presence of a c-kit mutation using DS was not an adverse prognostic factor (P= 0.355), but was a factor when using MB-PCR (P= 0.014). The presence of c-kit mutations with MB-PCR was also an independent adverse prognostic factor by multivariate analyses (P= 0.006). We conclude that sensitivity of c-kit mutation detection method is important to predict prognosis for t (8; 21) AML.