Chou Wen-Chien, Tang Jih-Luh, Lin Liang-In, Yao Ming, Tsay Woei, Chen Chien-Yuan, Wu Shang-Ju, Huang Chi-Fei, Chiou Rong-Jing, Tseng Mei-Hsuan, Lin Dong-Tsamn, Lin Kai-Hsin, Chen Yao-Chang, Tien Hwei-Fang
Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan.
Cancer Res. 2006 Mar 15;66(6):3310-6. doi: 10.1158/0008-5472.CAN-05-4316.
Nucleophosmin (NPM) mutations have been found in a significant proportion of adults with de novo acute myeloid leukemia (AML), especially in those of a normal karyotype. These results provide a basis for studies of the pathogenesis in this specific subgroup of AML. In this study, NPM mutations were analyzed in 173 Chinese patients of de novo AML, including adults and children. We found that NPM mutations were present in 19.1% of the overall population and 40.3% of those with a normal karyotype. Adults had a significantly higher incidence of NPM mutations than children [32 of 126 (25.4%) versus 1 of 47 (2.1%), P < 0.001]. NPM mutations were closely associated with normal karyotype (P < 0.001) and internal tandem duplication of FLT3 (P = 0.002), but negatively associated with CEBPA mutations (P = 0.032) and expression of CD34 (P < 0.001) and HLA-DR (P = 0.003). Serial analyses of NPM mutations showed the mutation disappeared at complete remission, but the same mutation reappeared at relapse, except for one who lost the mutation at the second relapse, when new cytogenetic abnormalities emerged. None acquired novel mutations during the follow-up period. In conclusion, NPM mutations occur in an age-dependent fashion. Moreover, the findings that NPM mutations are stable during disease evolution and closely associated with disease status make it a potential marker for monitoring minimal residual disease.
在相当比例的成人初发急性髓系白血病（AML）患者中发现了核磷蛋白（NPM）突变，尤其是那些核型正常的患者。这些结果为研究该特定AML亚组的发病机制提供了依据。在本研究中，对173例中国初发AML患者（包括成人和儿童）进行了NPM突变分析。我们发现，NPM突变存在于总体人群的19.1%以及核型正常患者的40.3%中。成人的NPM突变发生率显著高于儿童[126例中的32例（25.4%）对47例中的1例（2.1%），P<0.001]。NPM突变与核型正常（P<0.001）和FLT3内部串联重复（P = 0.002）密切相关，但与CEBPA突变（P = 0.032）以及CD34表达（P<0.001）和HLA-DR表达（P = 0.003）呈负相关。对NPM突变的系列分析显示，除了1例在第二次复发时出现新的细胞遗传学异常且失去该突变外，该突变在完全缓解时消失，但在复发时再次出现。在随访期间无人获得新的突变。总之，NPM突变以年龄依赖的方式发生。此外，NPM突变在疾病演变过程中稳定且与疾病状态密切相关的发现使其成为监测微小残留病的潜在标志物。
