急性髓系白血病患者NPM1、FLT3和C-KIT基因突变的检测及其预后分析

Detection of NPM1,FLT3and C-KIT Mutations in Acute Myeloid Leukemia and Their Prognostic Analysis

本研究旨在评估NPM1、FLT3和C-KIT基因突变在急性髓系白血病(AML)患者中的发生频率和对预后的影响,并探讨这些突变与临床特点、细胞遗传学及生存情况的关系。对我院2010年8月至2012年10月收治的78例初治AML患者,采用PCR扩增产物直接测序法或毛细管电泳法检测NPM1、FLT3和C-KIT基因的突变情况,了解这些突变阳性患者的临床特征。结果显示,NPM1突变患者在AML中的发生率为14.1%,在正常核型AML中的发生率为26.7%。NPM1基因突变者发病年龄偏高(P<0.05),外周血白细胞和血小板数高(P<0.05),CD34低表达(P<0.05),而在性别比例、骨髓原始细胞比例、血红蛋白浓度、CD117和HLA-DR表达水平、完全缓解(CR)率、总生存(OS)率、复发率方面差异无统计学意义(P>0.05)。78例AML患者中9例(11.5%)FLT3-ITD突变阳性,3例FLT3-TKD(3.8%)突变阳性,无同一患者同时发生这两种突变;FLT3-ITD突变者外周血白细胞和骨髓原始细胞比例较高(P<0.05),总生存率偏低(P<0.05),多见于正常核型(P<0.05),而在性别比例、年龄、外周血血小板数、血红蛋白浓度、完全缓解率、复发率方面差异无统计学意义(P>0.05)。FLT3-TKD突变例数较少,未单独进行统计学分析。6例(7.7%)C-KIT突变阳性。C-KIT突变在异常核型AML中的发生率较高(P<0.05),复发率较高(P<0.05),总生存率较低(P<0.05),而在性别、年龄、骨髓原始细胞比例、外周血象、完全缓解率方面差异无统计学意义(P>0.05)。结论:NPM1、FLT3和C-KIT突变检测有利于指导AML患者的治疗及预后评估。

This study was aimed to evaluate the frequencies and prognostic significance of the nucleophosmin 1 （NPM1） mutation, the fms-like tyrosine kinase 3 （FLT3） mutation and c-KIT mutation in acute myeloid leukemia （AML） and to explore their relevance to clinical characteristics, cytogenetics and survival. Genomic DNA from 78 newly dignosed AML from August 2010 to October 2012 was screened by PCR and sequencing or capillary electrophoresis （CE） for NPM1, FLT3 and c-KIT mutations. The results showed that the incidence of NPM1 mutation was 14.1% in AML patients and 26.7% in normal karyotype AML patients. NPM1 mutant cases were significantly associated with old age （ P 〈 0.05 ）, high peripheral white cell count and platelet counts （ P 〈 0.05 ） and low expression of CD34 （ P 〈 0.05 ）, but no statistic difference was found in sex, percentage of bone marrow blasts, Hb, expression of CD117 and HLA-DR, complete remission rate, overall survival and relapse rate（ P 〉 0.05 ）. The prevalences of FLT3-1TD and FLT3-TKD mutations were 11.5% （9/78） and 3.8% （3/78） respectively, and no one patient has both of the two mutations. Patients with FLT3-ITD mutation had higher white blood cell counts and percentage of in bone marrow blasts （ P 〈 0.05 ）, and lower overall survival（ P 〈 0.05 ）, more relative to normal karytype（ P 〈 0.05 ）, while no statistic difference was found in sex, age, platelet count, Hb level, complete remission rate and relapse rate （P 〉 0.05 ）. No stratistic analysis was performed due to the cases of less FLT3-TKD mutation. C-KIT mutation accounts for 7.7% （6/78）. Patients with C-KIT mutation had a higher percentage in abnormal karyotype（ P 〈 0.05 ）, and higher relapse rate （ P 〈 0.05 ）, and loweroverall survival, whereas no statistic difference was found in sex, age, percentage of bone marrow blasts, peripheral blood cell count, complete remission rate（ P 〉 0.05 ）. It is concluded that the detection of NPM1, FLT3 and C-KIT mutations may contribute to guiding treatment and evaluating prognosis of patients with AML.