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急性髓系白血病患者外周血细胞中FLT3基因表达与FLT3/ITD突变的关系及其意义

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

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【作者】 徐兵史鹏程宋小燕唐家宏周淑芸

【Author】 Bing Xu,Peng-Chang Shi,Xiao-Yan Song,Jia-Hong Tang and Shu-Yun ZhouDepartment of Hematology,Nanfang Hospital,Southern Medical University,Guangzhou,Guangdong,510515,P.R.China

【机构】 南方医科大学南方医院血液科

【摘要】 背景与目的:研究表明FLT3/ITD突变的急性髓性白血病(acute myeloid leukemia,AML)患者预后差,但关于AML患者FLT3基因的表达水平在预后中的作用及其与FLT3/ITD突变关系的研究尚不充分。本研究探讨初治AML患者FLT3基因的表达水平与FLT3/ITD突变的关系及其临床意义。方法:建立实时荧光定量PCR检测FLT3基因表达水平及PCR检测FLT3/ITD突变的方法,分析79例初治AML患者FLT3基因水平、FLT3/ITD突变及与预后的关系。结果:22.7%(18/79)的AML患者存在FLT3/ITD突变。92.4%(73/79)的患者标本中可检测到FLT3基因表达,FLT3基因表达水平为0~7320,中位数为312,正常对照组未检测到FLT3基因的表达。FLT3基因高表达及FLT3/ITD突变AML组的白细胞计数及骨髓白血病细胞均显著高于低表达和无突变AML组(P<0.05)。FLT3基因高表达的AML组FLT3/ITD突变率(25.6%)同低表达的AML组(20.0%)相比,差异无统计学意义(P>0.05),FLT3/ITD突变AML患者FLT3基因表达中位数与无突变组比较差异也无统计学意义。FLT3/ITD突变组的完全缓解率(58.8%)显著低于无FLT3/ITD突变组(82.1%)(P<0.05);FLT3基因高表达AML组FLT3/ITD的完全缓解率(68.6%)同低表达AML组(84.2%)相比差异无统计学意义(P>0.05),但无FLT3/ITD突变组中,FLT3基因高表达组完全缓解率(69.2%)显著低于低表达组(93.3%)(P<0.05)。结论:FLT3高表达与FLT3/ITD突变之间无明显相关性,FLT3高表达对于无FLT3/ITD突变AML患者可能是一个预后不良的指标。

【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.

【基金】 广东省科技计划项目(No.2004B30701005)~~
  • 【文献出处】 癌症 ,Chinese Journal of Cancer , 编辑部邮箱 ,2009年06期
  • 【分类号】R733.71
  • 【被引频次】2
  • 【下载频次】249
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