摘要目的 探讨伴有NPM1和FLT3-ITD基因突变急性髓系白血病(AML)患者的临床特点及其与疗效的关系.方法 采用PCR-毛细管电泳法对67例初诊AML患者进行NPM1基因突变和FLT3-ITD基因突变检测,并分析与疗效的关系.结果 NPM1突变阳性患者占所有AML患者的10.4％(7/67),占核型正常AML患者的26.1％ (6/23);FLT3-ITD基因突变阳性占所有AML患者的10.4％(7/67),占核型正常AML患者的17.4％(4/23).NPM1突变阳性患者和NPM1突变阴性患者相比,初诊时血小板计数(54.0× 109/L和27.5×109/L)差异有统计学意义(P＜0.01),AML-M5比例(57.1％与23.3％,P＜0.01)、CD34阳性患者比例(28.6％与63.3％)、染色体核型正常比例(85.7％与28.3％)、伴有特殊融合基因患者的比例(0和48.3％)、伴有FLT3-ITD突变阳性患者的比例(28.6％与8.3％)等指标差异均有统计学意义(P均＜0.01),在就诊时白细胞数、骨髓原始细胞比例、中位年龄、性别比例和完全缓解率方面差异无统计意义(P均＞0.05).而FLT3-ITD基因突变阳性患者就诊时白细胞数(26.9×109/L与8.1×109/L,P=0.013)和骨髓原始细胞比例(90％和76％,P=0.014)明显高于阴性患者.单独NPM1突变预后较好,但当合并FLT3-ITD突变时预后较差.结论 对初诊时核型正常AML患者检测NPM1和FLT3-ITD基因突变,有利于预后评估和指导治疗.

abstractsObjective To investigate the clinical characteristics and efficacy of acute myeloid leukemia (AML) with NPM1 and FLT3 mutations.Methods NPM1 and FLT3 mutations were detected in 67 patients with newly diagnosed AML by PCR-capillary electrophoresis.The relationship was analyzed between the mutations and efficacy.Results The incidence of NPM1 mutation was 10.4％ (7/67) in total AML patients and 26.1％ (6/23) in normal karyotypes AML patients.The incidence of FLT3-ITD mutation was 10.4％ (7/67) in total AML patients and 17.4％ (4/23) in normal karyotypes AML patients.The characteristics of 60 NPM1 wild type patients vs that of 7 NPMl mutation patients was as follow,platelet count (BPC) (54× 109/L vs.27.5 × 109/L,P ＜ 0.01),proportion of AML-M5 (57.1％ vs.27.3％,P ＜ 0.01),incidence of CD34+ (28.6％ vs.63.3％,P＜0.01),normal karyotypes (85.7％ vs.28.3％,P＜0.01),cases with particular fusion gene (0 vs.48.3％,P ＜ 0.01),incidence of FLt3-1TD-mutations positive (28.6％ vs.8.3％,P ＜ 0.01),and the differences were significant (P＜0.01).No statistic difference was found in white blood cell(WBC) counts,percentage of blasts in bone marrow,sex,median age and complete remission rate between the two groups (P ＞0.05).The WBC counts (26.9 × 109/L vs.8.1 × 109/L,P =0.013),percentage of blastsin in bone marrow (90％ vs.76％,P=0.014) in the FLT3-ITD mutationg positive patients were clearly higher than those in the FLT3-ITD negative patients.If not associated with FLT3-ITD mutations,mutant NPM1 appears to identify patients with improved response toward treatment.Conclusion It is necessary to detect NPM1 mutation and FLT3-ITD mutation in newly diagnosed AML patients,especially in patients with normal karyotype,which might help to molecular classification and treatment.