中文摘要：

目的分析急性髓细胞白血病（AML）的NPM1（Nucleophosmin）基因第12外显子突变,探索伴有NPM1基因突变的AML患者的临床特征。方法随机选择98份临床确诊的急性白血病和骨髓增生异常综合征（MDS）患者的冻存骨髓细胞标本,其中78份AML、10份急性淋巴细胞白血病（ALL）和10份MDS提取DNA,行多重PCR,同时扩增NPM1基因第12外显子及FLT3基因第14、15外显子,PCR-毛细管电泳同时检测NPM1和FLT3-ITD基因突变。结果 78例AML患者共检出21例（26.9%）具有NPM1基因突变,10例ALL和10例MDS均未检测出该突变。78例AML中52例核型正常,NPM1阳性19例（36.5%）,26例异常核型AML患者NPM1阳性仅2例（7.7%）,两组间差异有统计学意义（P〈0.05）。AML-M2、M5患者NPM1基因突变发生率高于其他组。NPM1突变型AML患者WBC中位数为42.0（16.3～102.0）×10^9/L,野生型为14.0（3.4～67.2）×10^9/L,两组间差异有统计学意义（P〈0.05）。21例NPM1突变型AML中12例（57.1%）同时伴有FLT3-ITD,57例NPM1野生型患者13例（22.8%）出现FLT3-ITD突变,两组间差异有统计学意义（P〈0.05）。NPM1阳性FLT3阴性患者9例中8例（88.9%）获得CR1,NPM1阳性FLT3阳性12例中3例（25%）获得CR1,NPM1阴性FLT3阴性33例中16例（48.5%）获得CR1,NPM1阴性FLT3阳性13例中2例（15.4%）获得CR1,组间差异有统计学意义（P〈0.05）。结论 NPM1基因突变是AML患者常见的一种突变,尤其是染色体核型正常AML患者发生率较高。伴有NPM1突变的AML患者的临床特征为年龄高,外周血白细胞高,更常见于M2和M5中,伴随FLT3-ITD突变发生率高,CR1率较高。

英文摘要：

Objective To analyze nucleophosmin （ NPM1） gene exon12 mutations in patients with acute myeloid leukemia（ AML） ,we explored the clinical characters of AML patients with NPM1 mutation. Methods Genomic DNAs from 98 acute leukemia and myelodysplastic syndrome （ MDS） patients were extracted,including 78 AML,10 ALL and 10 MDS. Genomic DNAs from all patients were amplified by multi-PCR for NPM1 exon 12 and FLT3 exon14,15,then screened gene mutations of NPM1 and FLT3 by PCR-capillary electrophoresis simultaneously. Results NPM1 gene mutations were present in 26. 9% of the overall 78 AML patients. There were no NPM1 gene mutation in 10 ALL and 10 MDS patients. NPM1 gene mutations were more prevelant in patients with normal karyotype-AML （ NK-AML） （ 19 /52,36. 5% ） compared with that in those with abnormal karyotype AML（ 2 /26,7. 7% ） （ P 〈0. 05）. NPM1 mutations were more frequently seen in M2 and M5 patients. NPM1 mutation cases were significantly associated with older age 53（ 18-77） vs. 43（ 17-73） ,P 〈0. 05,and high peripheral white cell counts 42. 0（ 16. 3-102. 0） × 10^9 /L vs. 14. 0 （ 3. 4-67. 2） × 10^9 /L,P 〈0. 05. FLT3-ITD mutation was more frequent inNPM1 mutant than wild cases （ 57. 1% vs. 22. 8% ,P 〈0. 05）. 8/9 NPM1 ＋ /FLT3-ITD -,3/12 NPM1 ＋ / FLT3-ITD ＋ ,16/33 NPM1 -/FLT3-ITD and 2/13 NPM1 -/FLT3-ITD ＋ patients gained CR1. Compared with the other groups,NPM1 ＋ /FLT3-ITD -patients owed higher CR1 （ P 〈0. 05）. Conclusions NPM1 gene mutations were the prevelant mutations in patients with AML,especially in those with NK-AML. The clinical characters of AML with NPM1 mutations were significantly associated with older age,high peripheral WBC,subtype M2,M5,high incidence of FLT3-ITD mutations and high CR1.