FLT3基因突变在急性早幼粒细胞白血病中的表达及临床意义  

Expression and clinical significance of FLT3 gene mutations in acute promyelocytic leukemia

作　　者：张娜 肖敏 Zhang Na;Xiao Min(Department of Hematology,Xijing Hospital of Air Force Medical University,Shaanxi Xi'an 710032,China;Department of Hematology,Tongji Hospital,Tongji Medical College of Huazhong University of Science and Technology,Hubei Wuhan 430030,China)

机构地区：[1]空军军医大学西京医院血液内科,陕西西安710032 [2]华中科技大学附属同济医学院同济医院血液内科,湖北武汉430030

出　　处：《现代肿瘤医学》2020年第6期1011-1015,共5页Journal of Modern Oncology

基　　金：国家自然科学基金项目(编号:81770211)

摘　　要：目的:检测急性早幼粒细胞白血病(acute promyelocytic leukemia,APL)患者FMS样酪氨酸激酶3(FLT3)基因内部串联重复(ITD)突变和酪氨酸激酶结构域(TKD)突变的表达,并探讨临床意义。方法:提取APL患者骨髓单个核细胞DNA,采用聚合酶链反应及测序技术检测FLT3-ITD和FLT3-TKD,分析临床资料及预后。结果:在77例APL患者中,23例(29.9%)检出FLT3-ITD,7例(9.1%)检出FLT3-TKD点突变,具体包括5例D835Y、1例N841I、1例D835Y和D835H复合杂合子。FLT3-ITD与高白细胞计数相关(P=0.033),而FLT3-TKD并无此相关性。与无FLT3基因突变患者相比,尽管FLT3-ITD和TKD突变患者的完全缓解率(CR)、总生存期(OS)、无事件生存期(EFS)均相对更差,除FLT3-TKD与缩短EFS显著相关(P=0.043)外,差异均无统计学意义。值得注意的是,无论是FLT3-ITD(P=0.011)还是FLT3-TKD(P=0.034)均提示高复发风险。多因素分析表明FLT3-ITD(HR=6.381,P=0.037)、FLT3-TKD(HR=5.198,P=0.009)、骨髓早幼粒细胞比例(HR=1.174,P=0.020)、高白细胞计数(WBC>10×10^9/L)(HR=9.067,P=0.011)可作为独立预后因素提示高复发风险。结论:FLT3-ITD和TKD在APL中均有表达,FLT3-ITD患者的白细胞计数高。虽然FLT3基因突变对APL患者的CR率和OS无显著影响,但可作为一个有价值的指标用于评估复发风险。Objective:To investigate the expression and prognostic value of FLT3-ITD and TKD in acute promyelocytic leukemia(APL).Methods:The DNA was extracted from mononuclear cells of bone marrow in APL patients.The expression of FLT3 gene mutations were examined by PCR,and the results were confirmed by sequencing.Clinical feature and prognosis were analyzed.Results:The incidence of FLT3-ITD and TKD mutations was 29.9%(23/77)and 9.1%(7/77,5 cases with D835Y,1 case with N841I and 1 case with D835Y and D835H).ITD was associated with high WBC count(P=0.033),but TKD was not.Both ITD and TKD mutation had no significant prognostic impact on CR rate and overall survival.However,TKD mutation was tend to indicate decreased event-free survival(P=0.043)and they were both associated with reduced relapse-free survival(FLT3-ITD,P=0.011.FLT3-TKD,P=0.034).In multivariate analysis,FLT3-ITD(HR=6.381,P=0.037),FLT3-TKD(HR=5.198,P=0.009),bone marrow blasts(HR=1.174,P=0.020),WBC>10×10^9/L(HR=9.067,P=0.011)were adverse factors for RFS.Conclusion:FLT3-ITD and TKD are both expressed in APL.Patients with FLT3-ITD have high WBC.Although FLT3 gene mutations have no significant prognostic impact on CR rate and OS,they can be used as valuable factors to evaluate the risk of relapse in APL.

关 键 词：急性早幼粒细胞白血病 FLT3-ITD FLT3-TKD 预后意义 

分 类 号：R733.7[医药卫生—肿瘤]