Nucleophosmin mutations in Chinese adults with acute myelogenous leukemia
Nucleophosmin mutations in Chinese adults with acute myelogenous leukemia
复制标题
中国成人急性髓系白血病的核磷蛋白突变
DOI：
10.1007/s00277-008-0591-8
复制
发表时间：
2009-02-01
影响因子：
3.5
通讯作者：
Huang, Xiao-Jun
中科院分区：
文献类型：
--
作者：
Ruan, Guo-Rui;Li, Jin-Lan;Huang, Xiao-Jun
最近，在50 - 60%的成人急性髓细胞性白血病（AML）患者中检测到核磷蛋白（NPM1）基因突变，主要是正常核型。本研究采用实时荧光定量聚合酶链反应（real-time quantitative polymerase chain reaction，RQ-PCR）结合序列分析技术，检测中国AML患者中典型的NPM1基因突变（A、B、D型）。220例AML患者中NPM1突变的检出率为16.4%，其中107例（14.2%）为法美英（FAB）亚型M2，43例（2.3%）为M3，52例（30.8%）为M4/M5。在4例M0、7例M1、5例M6和2例M7病例中仅检测到1例NPM1突变。8例患者在治疗后随访，5例血液学缓解患者在随访2 - 14个月内继续检测NPM1突变阴性。序列分析显示36例阳性病例均为杂合突变，其中29例（80.6%）为A型，4例（11.1%）为B型，1例罕见DD-3突变。我们还检测到两个新的突变，即CTCG和CAAG插入，分别命名为BJ-01和BJ-02。此外，38.9%（14/36）的NPM1突变患者同时表现出FLT3基因的内部串联重复，66.7%（22/33）的患者不表达CD34。结果表明，RQ-PCR是一种可靠、灵敏的检测NPM1突变的方法，可用于AML的筛查和微小残留病的定量分析。
Recently, mutations in the nucleophosmin (NPM1) gene were detected in 50-60% of adult acute myelogenous leukemia (AML) patients, mainly with a normal karyotype. In this study, we detected typical NPM1 mutations (types A, B, D) in untreated Chinese AML patients using real-time quantitative polymerase chain reaction (RQ-PCR) followed by sequence analysis. The detection rate of NPM1 mutations in 220 AML patients was 16.4%, including 107 (14.2%) with the French-American-British (FAB) subtype M2, 43 (2.3%) with M3, and 52 (30.8%) with M4/M5. Only one case each with an NPM1 mutation was detected in four M0, seven M1, five M6, and two M7 cases. Eight patients were followed up after treatment, and five patients in hematologic remission continued to test negative for NPM1 mutations within 2-14 months of follow-up. Sequence analysis revealed that all the 36 positive cases were heterozygous for the mutation with 4-bp insertions at nt 959; the 36 cases included 29 (80.6%) cases with type A, four (11.1%) cases with type B, and one rare DD-3 mutation. We also detected two new mutations, namely, CTCG and CAAG insertions, named BJ-01 and BJ-02, respectively. Further, 38.9% (14/36) patients with NPM1 mutations simultaneously exhibited internal tandem duplications in the FLT3 gene, and 66.7% (22/33) patients did not express CD34. The results demonstrated that RQ-PCR was a reliable and sensitive method for detecting NPM1 mutations, for screening AML, and for the quantitative analysis of minimal residual diseases.