AML1-ETO9a is correlated with C-KIT overexpression/mutations and indicates poor disease outcome in t(8;21) acute myeloid leukemia-M2
AML1-ETO9a is correlated with C-KIT overexpression/mutations and indicates poor disease outcome in t(8;21) acute myeloid leukemia-M2
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AML1-ETO9a 与 C-KIT 过度表达/突变相关，表明 t(8;21) 急性髓系白血病-M2 的疾病结果不佳
DOI：
10.1038/leu.2009.104
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发表时间：
2009-09-01
期刊：
影响因子：
11.4
通讯作者：
Chen, S-J
中科院分区：
文献类型：
--
作者：
Jiao, B.;Wu, C-F;Chen, S-J
AML1-ETO融合基因主要由t(8；21)易位产生，主要见于急性髓系白血病M2亚型(AML-M2)。其剪接变异体转录本AML1-ETO9a可快速诱发小鼠模型白血病。为探讨AML1-ETO9a在t(8；21)AML-M2中的表达及其临床意义，采用定性和巢式逆转录聚合酶链式反应(RT-PCR)方法检测了118例t(8；21)AML-M2患者AML1-ETO9a的表达。将这些病例分为AML1-ETO9a-H组(86例，定性RT-PCR阳性，定量RT-PCR检测AML1-ETO9a水平较高)和AML1-ETO9a-L组(32例，定性RT-PCR阴性，定量RT-PCR检测AML1-ETO9a水平较低，但仍可检测到)。与AML1-ETO9a-L组相比，AML1-ETO9a-H组c-kit表达显著增加。在36例C-KIT突变患者中，32例AML1-ETO9a过度表达(P=0.0209)。临床上，AML1-ETO9a-H患者外周血白细胞数明显升高，骨髓异常粒细胞减少，CD56升高，CD19表达降低(P=0.0451，P=0.0479，P=0.0149，P=0.0298)。此外，AML1-ETO9a的过表达与患者的无事件生存期和总生存期有关(P=0.0072和P=0.0076)。综上所述，这些数据提示AML1-ETO9a与C-kit过度表达/突变相关，并提示t(8；21)AML-M2患者预后不良。
AML1-ETO fusion gene is generated from chromosomal translocation t(8;21) mainly in acute myeloid leukemia M2 subtype (AML-M2). Its spliced variant transcript, AML1-ETO9a, rapidly induces leukemia in murine model. To evaluate its clinical significance, AML1-ETO9a expression was assessed in 118 patients with t(8;21) AML-M2, using qualitative and nested quantitative reverse transcriptase (RT)–PCR methods. These cases were accordingly divided into the AML1-ETO9a-H group (n=86, positive for qualitative RT–PCR, with higher level of AML1-ETO9a by quantitative RT–PCR) and the AML1-ETO9a-L group (n=32, negative for qualitative RT–PCR, with lower but still detectable level of AML1-ETO9a by quantitative RT–PCR). C-KIT expression was significantly increased in the AML1-ETO9a-H group, as compared with the AML1-ETO9a-L group. Of the 36 patients harboring C-KIT mutations, 32 patients overexpressed AML1-ETO9a (P=0.0209). Clinically, AML1-ETO9a-H patients exhibited significantly elevated white blood cells count, less bone marrow aberrant myelocytes, increased CD56 but decreased CD19 expression (P=0.0451, P=0.0479, P=0.0149 and P=0.0298, respectively). Moreover, AML1-ETO9a overexpression was related to short event-free and overall survival time (P=0.0072 and P=0.0076, respectively). Taken together, these data suggest that AML1-ETO9a is correlated with C-KIT overexpression/mutations and indicates poor disease outcome in t(8;21) AML-M2.