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急性髓系白血病患者外周血中Fms样酪氨酸激酶3(FLT3)基因表达与FLT3内部串联重复突变的相关性

[Correlation of Fms-like tyrosine kinase 3 (FLT3) gene expression to FLT3/internal tandem duplication mutation in peripheral blood of acute myeloid leukemia.].

作者信息

Xu Bing, Shi Peng-Chang, Song Xiao-Yan, Tang Jia-Hong, Zhou Shu-Yun

机构信息

Department of Hematology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, 510515, P.R. China.

出版信息

Ai Zheng. 2009 Jun;28(6):632-6.

Abstract

BACKGROUND AND OBJECTIVE

Fms-like tyrosine kinase 3 internal tandem duplication (FLT3/ITD) is associated with an unfavorable prognosis in acute myeloid leukemia (AML). However, the role of FLT3 expression as well as its correlation to FLT3/ITD has not sufficiently studied. This study was to evaluate the relationship between FLT3 gene expression and FLT3/ITD mutation in patients with de novo AML.

METHODS

FLT3 gene expression was determined by real-time quantitative polymerase chain reaction (RQ-PCR). FLT3/ITD mutation was detected by PCR in 79 de novo AML patients.

RESULTS

FLT3/ITD mutations were found in 22.8% (18/79) patients. FLT3 gene expression (range: 0-7320, median: 312) was detected in 92.4% (73/79) patients, but not in normal controls. Compared to AML patients with low FLT3 expressers and without FLT3/ITD mutation, patients with high FLT3 expressers and FLT3/ITD mutation had a significantly higher white blood count as well as a higher ratio of bone marrow blasts. The positive rate of FLT3/ITD mutation was not correlated to the level of FLT3 expression, and no statistical difference of FLT3 expression was found between AML patients with and without FLT3/ITD mutation. The complete remission (CR) rate of AML patients with FLT3/ITD mutation (58.8%) was significance lower than that of those without FLT3/ITD mutation (82.1%). In AML patients without FLT3/ITD mutation, the CR rate was significantly lower in patients with high FLT3 expressers (69.2%) than in those with low FLT3 expressers (93.3%).

CONCLUSION

The FLT3 expression is not associated with FLT3/ITD mutation. High-FLT3 expression may be a poor prognostic factor for AML patients without FLT3/ITD mutation.

摘要

背景与目的

Fms样酪氨酸激酶3内部串联重复(FLT3/ITD)与急性髓系白血病(AML)的不良预后相关。然而,FLT3表达的作用及其与FLT3/ITD的相关性尚未得到充分研究。本研究旨在评估初发AML患者中FLT3基因表达与FLT3/ITD突变之间的关系。

方法

采用实时定量聚合酶链反应(RQ-PCR)测定FLT3基因表达。通过PCR检测79例初发AML患者的FLT3/ITD突变。

结果

22.8%(18/79)的患者检测到FLT3/ITD突变。92.4%(73/79)的患者检测到FLT3基因表达(范围:0 - 7320,中位数:312),而正常对照未检测到。与FLT3低表达且无FLT3/ITD突变的AML患者相比,FLT3高表达且有FLT3/ITD突变的患者白细胞计数显著更高,骨髓原始细胞比例也更高。FLT3/ITD突变的阳性率与FLT3表达水平无关,有FLT3/ITD突变和无FLT3/ITD突变的AML患者之间FLT3表达无统计学差异。FLT3/ITD突变的AML患者完全缓解(CR)率(58.8%)显著低于无FLT3/ITD突变的患者(82.1%)。在无FLT3/ITD突变的AML患者中,FLT3高表达患者的CR率(69.2%)显著低于FLT3低表达患者(93.3%)。

结论

FLT3表达与FLT3/ITD突变无关。高FLT3表达可能是无FLT3/ITD突变的AML患者的不良预后因素。

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