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[急性髓系白血病中FLT3基因表达水平与内部串联重复突变的相关性及其临床意义]

[Correlation of FLT3 gene expression level and internal tandem duplication mutation in acute myeloid leukemia and its clinical significance].

作者信息

Wang Yun-gui, Liu Xu-hui, Liang Yi, Jin Jie

机构信息

Department of Hematology, The First Affiliated Hospital, Institute of Hematology, Zhejiang University, Hangzhou 310003, China.

出版信息

Zhonghua Xue Ye Xue Za Zhi. 2008 Nov;29(11):741-5.

Abstract

OBJECTIVE

To evaluate the prevalence of FLT3 gene expression and internal tandem duplication (ITD) mutation in acute myeloid leukemia (AML) patients and its clinical significance.

METHODS

The expression level of FLT3 mRNA was detected with real-time quantitative RT-PCR (RQ-PCR) technique in 152 bone marrow samples from 129 AML patients. The ITD of the FLT3 gene (FLT3/ITD) was detected in 75 de novo AML patients by reverse transcription polymerase chain reaction (RT-PCR).

RESULTS

The expression levels of FLT3 mRNA was 0.0020(0.0006 - 0.0040) in normal controls, and 0.1041 (0 - 33.8736) in 80 de novo AML patients (P = 0.001). FLT3/ITDs were found in 11 (14.7%) of 75 de novo AML patients. The FLT3 expression levels in patients with FLT3/ITD were 0.0297 to 33.8736 with a median level of 0.2200, and in those without FLT3/ITD were 0 to 26.2200 with a median level of 0.0975. The FLT3 expression levels in the former patients were higher than that in the latter ones, but there was no statistical significance (P = 0.093). The complete remission (CR) rate was lower in acute promyelocytic leukemia (APL) patients with FLT3/ITD than in APL patients without FLT3/ITD (P = 0.015). In de novo AML other than APL patients without FLT3/ITD, the CR rate was lower in patients with higher levels of FLT3 expression (expression level > 0.04, CR rate 37.5%) than those with lower levels of FLT3 expression (expression level < 0.04, CR rate 100%). On follow-up of 20 patients, the FLT3 expression level was decreased at least one logarithm degree when they got CR, but it was no significant change in non-remission patients.

CONCLUSIONS

Quantification of FLT3 mRNA expression level and detection of FLT3/ITD in AML patients may serve as an index for evaluating therapeutic efficacy, predicting prognosis, and monitoring minimal residual disease.

摘要

目的

评估急性髓系白血病(AML)患者中FLT3基因表达及内部串联重复(ITD)突变的发生率及其临床意义。

方法

采用实时定量逆转录聚合酶链反应(RQ-PCR)技术检测129例AML患者152份骨髓样本中FLT3 mRNA的表达水平。采用逆转录聚合酶链反应(RT-PCR)检测75例初发AML患者的FLT3基因ITD(FLT3/ITD)。

结果

正常对照中FLT3 mRNA表达水平为0.0020(0.0006 - 0.0040),80例初发AML患者中为0.1041(0 - 33.8736)(P = 0.001)。75例初发AML患者中有11例(14.7%)检测到FLT3/ITD。FLT3/ITD患者的FLT3表达水平为0.0297至33.8736,中位数为0.2200,未检测到FLT3/ITD患者的FLT3表达水平为0至26.2200,中位数为0.0975。前者的FLT3表达水平高于后者,但差异无统计学意义(P = 0.093)。FLT3/ITD的急性早幼粒细胞白血病(APL)患者的完全缓解(CR)率低于未检测到FLT3/ITD的APL患者(P = 0.015)。在初发非APL且未检测到FLT3/ITD的AML患者中,FLT3表达水平较高(表达水平>0.04,CR率37.5%)的患者的CR率低于FLT3表达水平较低(表达水平<0.04,CR率100%)的患者。对20例患者进行随访,CR时FLT3表达水平至少下降一个对数级,但未缓解患者无明显变化。

结论

AML患者FLT3 mRNA表达水平的定量及FLT3/ITD的检测可作为评估治疗效果、预测预后及监测微小残留病的指标。

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