CD13表达及其与FLT3-ITD、NPM1突变在急性髓系白血病中的研究  

Analysis of CD13 expression and mutations of FLT3-ITD and NPM1 in patients with acute myeloid leukemia

作　　者：周琛[1] 李东[1] 张凡[1] 乔纯 环亚红[1] 宋艳智 董平[1] 夏素琴[1] 王琼[1] 李翠萍[1] 张苏江 李建勇 卢应连 廖海英[1] 隋雪梅[1] 

机构地区：[1]南京明基医院南京医科大学附属医院血液科,南京210019 [2]南京医科大学第一附属医院江苏省人民医院血液科,南京210019

出　　处：《重庆医科大学学报》2016年第4期398-403,共6页Journal of Chongqing Medical University

基　　金：南京医科大学科技发展基金资助项目(编号:2011NJMU223)

摘　　要：目的:探讨72例急性髓系白血病(acute myelogenous leukemia,AML)患者CD13表达及其与FLT3-ITD、NPM1突变同步检测的临床意义,并分析FLT3-ITD、NPM1突变的关系及其与CD13表达水平的相关性。方法:收集72例AML患者病例资料,采用流式细胞仪检测72例AML患者CD13表达,PCR及Sanger测序法检测FLT3-ITD、NPM1突变。结果:72例AML患者中68例CD13表达阳性(68/72,94.44%),经诱导化疗,44例获得完全缓解(44/68,64.71%)。CD13^+与CD13-患者相比,χ~2=2.118,P=0.148,完全缓解率差异无统计学意义(P>0.05)。68例CD13^+的AML患者中,FLT3-ITD^+/NPM1^+双突变患者白细胞计数明显高于其余3组,差异均有统计学意义(P=0.000、P=0.010、P=0.000),而完全缓解率明显低于FLT3-ITD^-/NPM1^+与FLT3-ITD^-/NPM1^-组,差异有统计学意义(χ~2=8.400,P=0.000;χ~2=8.880,P=0.000)。FLT3-ITD^+/NPM1^-患者中位生存期仅为24个月,较FLT3-ITD^-/NPM1^+与FLT3-ITD^-/NPM1^-患者,生存期更短。FLT3-ITD^-/NPM1^+患者的平均年龄、白细胞计数及血红蛋白均高于FLT3-ITD^+/NPM1^-患者(P=0.030;P=0.000;P=0.040),白细胞计数及血红蛋白均高于FLT3-ITD^-/NPM1^-患者(P=0.020;P=0.00),完全缓解为85.71%,明显高于FLT3-ITD^+/NPM1^+和FLT3-ITD^+/NPM1^-患者(χ2=8.40,P=0.000;χ2=13.45,P=0.000),中位生存期为41个月(95%CI=34.4~47.6个月),较FLT3-ITD^+/NPM1^+和FLT3-ITD^+/NPM1^-患者生存期长,提示NPM1突变患者预后良好。结论:68例CD13^+患者中,FLT3-ITD^+/NPM1^+双突变患者具有高白细胞数和低CR率;FLT3-ITD^+/NPM1^-患者生存期短;FLT3-ITD^-/NPM1^+患者诱导缓解率高,FLT3-ITD^+/NPM1^-较低。对于AML患者,提示可以同时分析CD13表达及FLT3-ITD和NPM1突变的情况,为AML的相关治疗提供一个更好的思路。Objective：To explore the clinical implications of CD13 expression level and the mutation of FLT3-ITD and NPM1 gene in72 acute myeloid leukemia（AML）patients. Methods：Clinical features（blood routine and CR rate）of 72 AML patients were collected.The CD13 expression level was analyzed by flow cytometry and the mutations of FLT3-ITD and NPM1 were detected by polymerase chain reaction（PCR） as well as Sanger sequencing. Results：Totally 68（94.44%） out of 72 AML cases had CD13 expression in leukemia cells;44（64.71%）out of 72 AML cases had complete remission after induction chemotherapy. No statistical difference was found between CD13~＋and CD13-patients（P 0.05）. Among 68 CD13~＋ AML patients,WBC count was higher in patients with FLT3-ITD~＋/NPM1~＋mutations than in other groups,with statistical differences（P=0.000;P=0.010;P=0.000）and CR rate was lower in patients with FLT3-ITD~＋/NPM1~＋mutations than in patients with FLT3-ITD^-/NPM1~＋and FLT3-ITD^-/NPM1^- （χ2=8.400,P=0.000;χ2=8.88,P=0.000）. The median overall survival of FLT3-ITD~＋/NPM1^- patients was 24 months,shorter than that of FLT3-ITD^-/NPM1~＋and FLT3-ITD^-/NPM1^- patients. FLT3-ITD^-/NPM1~＋patients was older than FLT3-ITD~＋/NPM1^- patients and had highe WBC and hemoglobin count（P =0.030;P =0.000;P =0.040）. FLT3-ITD^-/NPM1 ~＋ patients had higher WBC and hemoglobin coun than FLT3-ITD^-/NPM1^- patients（P=0.020;P=0.000）. The CR rate was 85.71%,apparently higher than those of FLT3-ITD~＋/NPM1 and FLT3-ITD~＋/NPM1^- patients（χ2=8.400,P=0.000;χ2=13.450,P=0.000）. The median overall survival was 41 months,longer tha those of FLT3-ITD~＋/NPM1~＋and FLT3-ITD~＋/NPM1^- patients. All of these presented a favorable prognosis in FLT3-ITD^-/NPM1~＋patients. Conclusion：In 68 CD13~＋ patients,FLT3-ITD~＋/NPM1~＋ patients have higher WBC count and lower CR rate. FLT3-ITD~＋/NPM1 patients have shorter survival. FLT3-ITD^-/NPM1~＋patients have higher remission rate than FLT3-ITD~＋/NPM1^- patients.

关 键 词：CD13 FLT3-ITD突变 NPM1突变 急性髓系白血病 预后 

分 类 号：R733.7[医药卫生—肿瘤]