骨髓异常增生综合征酪氨酸激酶受体FLT3和c-KIT基因表达异常的研究

c-KIT and tyrosine kinase receptor FLT3 mutations in myelodysplastic syndrome

目的:本研究旨在检测骨髓异常增生综合征(MDS)患者骨髓中酪氨酸激酶受体FLT3、c-KIT基因表达水平及FLT3-LM,以讨论FLT3、c-KIT受体对于MDS患者的临床意义。方法:收集38例诊断明确的MDS患者及10例非恶性血液病患者的骨髓并提取单个核细胞,应用PCR检测FLT3基因表达水平及FLT3基因长度突变(FLT3-LM);应用逆转录聚合酶链反应(RT-PCR)检测c-KIT基因表达水平。结果:38例MDS患者骨髓单个核细胞有11例检测到FLT3基因表达,而对照组均未有FLT3基因表达,2者差异有统计学意义(P<0.05)。11例FLT3受体表达阳性患者中有2例存在FLT3-LM,阳性率为18.2%,10例对照均未发现FLT3-LM。38例MDS患者中有7例检测到c-KIT基因表达,而10例对照组均未有c-KIT基因表达,阳性率为18.4%,2者差异有统计学意义(P<0.05),且FLT3-LM、c-KIT基因表达多为高危患者。结论:以上研究显示MDS患者存在FLT3、c-KIT基因表达异常,且FLT3-LM、c-KIT(+)多发生在高危患者。提示酪氨酸激酶受体FLT3、c-KIT基因表达异常对于MDS患者病情及预后判断中有重要作用。

Objective:This study is to investigate tyrosine kinase receptor FLT3 and c-KIT receptor expression and FLT3 length mutation (FLT3-LM) in the patients with myelodysplastic syndrome (MDS) and their clinical implication.Method:Analysis of FLT3-LM was performed on bone marrow samples from 38 patients with MDS by PCR and c-KIT gene expression by RT-PCR.Result:Eleven FLT-3 gene expression (28.9%) were found in 38 patients with myelodysplastic syndrome,compared with no expression in 10 controls (P<0.05). We also found 7 c-KIT receptor expression in 38 patients with MDS. No c-KIT gene expression was found in 10 controls. FLT3-LM were detected in 2 of 11 MDS patients (18.2%),while no FLT3-LM was detected in controls. The expression rate of c-KIT was 18.4% (7 of 38) in MDS patients in comparision with no expression in controls(P<0.05). Most of the patients with FLT3-LM and c-KIT expression were high-risk patients.Conclusion:FLT3 mututions and c-KIT expression represent genetic abnormalities in MDS patients. Higher FLT3-LM and c-KIT expression were found in high-risk MDS patients. FLT3 aberration and c-KIT expression could be helpful to recognize the disease severity and prognosis of MDS patients.