Analysis of NPM1 Gene Mutations in Chinese Adults with Acute Myeloid Leukemia
Analysis of NPM1 Gene Mutations in Chinese Adults with Acute Myeloid Leukemia
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DOI：
10.1532/ijh97.a10620
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发表时间：
2007-08
影响因子：
2.1
通讯作者：
Lingzhi Yan;Suning Chen;Jian-ying Liang;Yu-feng Feng;J. Cen;Jun He;Wei-rong Chang;Zi-ling Zhu;Jinlan Pan;Ya-fang Wu;Yongquan Xue;Depei Wu
中科院分区：
文献类型：
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作者：
Lingzhi Yan;Suning Chen;Jian-ying Liang;Yu-feng Feng;J. Cen;Jun He;Wei-rong Chang;Zi-ling Zhu;Jinlan Pan;Ya-fang Wu;Yongquan Xue;Depei Wu
许多欧洲研究小组最近发现，核磷蛋白（NPM1）基因外显子12的突变是急性髓性白血病（AML）患者中最常见的遗传病变，特别是在核型正常的情况下。本研究探讨了156名中国成人AML患者中NPM1突变的患病率和临床特征。利用基因组DNA聚合酶链反应产物的直接测序或片段分析检测NPM1外显子12突变。NPM1突变占总人群的28.2%，其中M0为1/1 (100%)，M1为11/27 (40.7%)，M2为11/46 (23.9%)，M3为0/29 (0%)，M4为2/9 (22.2%)，M5为18/39 (46.2%)，M6为1/5（20.0%）。与核型异常患者（66例中有7例，10.6%,P < 0.001）相比，核型正常患者（90例中有37例，41.1%）的NPM1基因突变更为普遍。对25例npm1突变病例的序列分析显示了已知的突变（A型、D型、NM型和PM型）以及一种新的序列变异（这里称为S型）。所有突变型均为杂合型，并有一个4bp的插入。NPM1突变与老年（P < 0.05）、外周血白细胞计数高（P < 0.05）、法国-美国-英国M1/M5亚型相关，与CD34、CD117表达负相关（P < 0.05）。因此，本研究提供了中国人群NPM1外显子-12突变检测方法及相关临床资料。
Many European groups have recently described that mutations at exon-12 of the nucleophosmin (NPM1) gene are the most frequent genetic lesion in patients with acute myeloid leukemia (AML), especially in the presence of a normal karyotype. This study explored the prevalence and clinical profile of NPM1 mutations in a cohort of 156 Chinese adults with AML. NPM1 exon-12 mutations were detected using direct sequencing or fragment analysis of genomic DNA polymerase chain reaction products. NPM1 mutations were present in 28.2% of the overall population, including 1/1 (100%) of M0, 11/27 (40.7%) of M1, 11/46 (23.9%) of M2,0/29 (0%) of M3,2/9 (22.2%) of M4,18/39 (46.2%) of M5, and 1/5 (20.0%) of M6. NPM1 gene mutations were more prevalent in patients with a normal karyotype (37 of 90; 41.1%) when compared with patients with karyotypic abnormalities (7 of 66; 10.6%;P <.001). Sequence analysis of 25 NPM1-mutated cases revealed known mutations (type A, D, NM, and PM) as well as one novel sequence variation (here named as type S). All mutational types were heterozygous and showed a 4 bp insertion. NPM1 mutations were significantly associated with old age (P <.05), high peripheral white blood cell count (P <.05), and the subtypes of French-American-British categories M1/M5, but negatively associated with expression of CD34 (P <.05) and CD117 (P <.05). Thus, this study provides the methods of NPM1 exon-12 mutations detection and related clinical data of NPM1 mutated cases in a Chinese population.