FLT3基因的表达对于急性髓系白血病的调控作用初探

Preliminary study on the regulation of acute myeloid leukemia by FLT3 gene expression

目的从细胞实验和临床病例两个层面探讨FLT3表达对急性髓系白血病(AML)患者预后的影响。方法选取2012年1月至2017年6月就诊于四川大学华西医院的AML初诊患者为研究对象。构建FLT3过表达和干扰表达的AML细胞模型,检测促细胞凋亡基因BAK基因及蛋白表达水平,检测白血病细胞的增殖和凋亡情况。检测临床初诊的AML患者骨髓标本中FLT3的表达及FLT3-ITD变异,并随访患者的预后。结果细胞实验显示,FLT3过表达的AML细胞中BAK基因及蛋白表达水平均低于干扰表达组(P<0.001),FLT3过表达的AML细胞增殖高于干扰表达组(P<0.001),细胞凋亡率低于干扰表达组(P<0.001)。AML初诊患者FLT3表达水平高于健康对照(P<0.001)。FLT3-ITD阳性AML患者的FLT3表达水平显著高于野生型(P=0.002)。生存分析结果显示,中风险组中FLT3高表达AML患者的完全缓解率及总体生存率低于低表达患者(P<0.001)。结论FLT3过表达可能通过促进白血病细胞增殖,抑制其凋亡从而影响AML的病程和患者的预后,可能是AML预后的不良因素。

ObjectiveTo assess the influence of FLT3 expression on the prognosis of patients with acute myeloid leukemia(AML)by cell experiment and clinical data analysis.MethodsModels for FLT3 over-expression and interference-expression in AML cells were constructed.The level of BAK gene expression and its protein product was determined,along with the proliferation and apoptosis of leukemia cells.FLT3 gene expression and FLT3-ITD variant were determined among patients with newly diagnosed AML.ResultsCompared with the interference-expression group,the level of BAK gene expression and its protein in FLT3 over-expression AML cells was significantly lower(P<0.001),which also showed significantly faster proliferation(P<0.001)and lower rate of apoptosis(P<0.001).The expression level of FLT3 gene among patients with newly diagnosed AML was also significantly higher compared with the healthy controls(P<0.001).The FLT3 gene expression of FLT3-ITD positive AML patients was higher than that of FLT3-WT patients(P=0.002).Survival analysis showed that AML patients with high FLT3 expression in the medium-risk group had a lower complete remission rate and overall survival rate compared with those with a low FLT3 expression(P<0.001).ConclusionOver-expression of FLT3 may influence the course of AML by promoting the proliferation of leukemia cells and inhibiting their apoptosis,which in turn may affect the prognosis of patients and serve as a negative prognostic factor for AML.