High expression of c-kit mRNA predicts unfavorable outcome in adult patients with t(8;21) acute myeloid leukemia.
High expression of c-kit mRNA predicts unfavorable outcome in adult patients with t(8;21) acute myeloid leukemia.
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c-kit mRNA 高表达预示 t (8;21) 急性髓系白血病成年患者的不良结果
DOI：
10.1371/journal.pone.0124241
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发表时间：
2015
期刊：
影响因子：
3.7
通讯作者：
Yu L
中科院分区：
文献类型：
--
作者：
Gao X;Lin J;Gao L;Deng A;Lu X;Li Y;Wang L;Yu L
t（8;21）易位（产生AML 1/ETO融合基因）的急性髓性白血病（AML）患者的某些亚组显示出较差的存活率的原因仍然是难以捉摸的。原癌基因c-kit在大约80%的AML病例中表达。c-kit基因的激酶结构域突变是与t（8;21）AML相关的最常见的功能获得性突变之一，预示着较高的复发风险和不良预后。然而，c-kit高表达在t（8;21）AML中的作用仍然知之甚少。在这里，我们评估了AML患者中c-kit表达水平的预后意义。采用实时荧光定量逆转录聚合酶链反应（real-time quantitative reverse transcription PCR，RT-PCR）检测132例成人AML患者c-kit mRNA的表达。根据c-kit表达水平将患者分组为四分位数（Q1-Q4，每个四分位数包含25%的患者），并分为c-kit高（Q4; n = 33）和c-kit低（Q1-Q3; n = 99）。c-kit高表达与AML 1/ETO阳性和c-kit突变相关。值得注意的是，35.8%携带野生型c-kit的AML 1/ETO阳性AML患者表达高水平的c-kit，表明其他因素参与了c-kit的过度表达。在AML 1/ETO阳性患者中，高c-kit表达与较差的总生存期和无事件生存期相关，并且在多变量分析中以c-kit突变独立的方式独立预测总生存期和无事件生存期。因此，高c-kit表达可作为预后不良的可靠分子标志物，支持c-kit信号传导在AML 1/ETO阳性AML中的发病作用。AML 1/ETO阳性且c-kit高表达的患者可能受益于早期治疗调整和分子靶向治疗。
The reason that a certain subgroup of acute myeloid leukemia (AML) patients with t(8;21) translocation (generating the AML1/ETO fusion gene) displays a poor survival remains elusive. The proto-oncogene c-kit is expressed in approximately 80% of AML cases. The kinase domain mutation of the c-kit gene, one of the most common gain-of-function mutations associated with t(8;21) AML, predicts higher relapse risk and poor prognosis. However, the role of c-kit high expression in t(8;21) AML remains poorly understood. Here we evaluated the prognostic significance of c-kit expression levels in AML patients. The mRNA expression of c-kit was determined by real-time quantitative reverse transcription PCR in 132 adult AML patients. Patients were grouped into quartiles according to c-kit expression levels (Q1–Q4, each quartile containing 25% of patients) and divided into c-kit high (Q4; n = 33) and c-kit low (Q1–Q3; n = 99). High c-kit expression was associated with AML1/ETO-positive and with c-kit mutation. Of note, 35.8% of the AML1/ETO-positive AML patients carrying wild-type c-kit expressed high levels of c-kit, suggesting that other factors are involved in c-kit overexpression. High c-kit expression was associated with inferior overall and event-free survival in AML1/ETO-positive patients and was independently predictive for overall and event-free survival in multivariate analyses in a c-kit mutation-independent manner. Thus, high c-kit expression serves as a reliable molecular marker for poor prognosis, supporting a pathogenetic role of c-kit signaling in AML1/ETO-positive AML. AML1/ETO-positive patients with high c-kit expression might benefit from early treatment modifications and molecular target therapies.
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