Nucleophosmin mutations in De novo acute myeloid leukemia:: The age-dependent incidences and the stability during disease
Nucleophosmin mutations in De novo acute myeloid leukemia:: The age-dependent incidences and the stability during disease
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DOI：
10.1158/0008-5472.can-05-4316
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发表时间：
2006-03-15
期刊：
影响因子：
11.2
通讯作者：
Tien, HF
中科院分区：
文献类型：
--
作者：
Chou, WC;Tang, JL;Tien, HF
核磷蛋白（NPM）突变已被发现在一个显着比例的成人新发急性髓性白血病（AML），特别是在那些正常核型。这些结果为研究这一特定急性髓细胞白血病亚组的发病机制提供了基础。本研究分析了173例中国初治AML患者（包括成人和儿童）的APM突变。我们发现，NPM突变存在于19.1%的总人口和40.3%的正常核型。成人NPM突变发生率显著高于儿童[32/126（25.4%）vs 1/47（2.1%），P < 0.001]。ATPM突变与正常核型（P < 0.001）和FLT 3内部串联重复（P = 0.002）密切相关，而与CEBPA突变（P = 0.032）、CD 34（P < 0.001）和HLA-DR（P = 0.003）表达呈负相关。APM突变的系列分析显示，突变在完全缓解时消失，但相同的突变在复发时再次出现，除了一个在第二次复发时失去突变的人，当新的细胞遗传学异常出现时。在随访期间没有获得新的突变。总之，NPM突变以年龄依赖的方式发生。此外，ATPM突变在疾病演变过程中是稳定的，并与疾病状态密切相关，这一发现使其成为监测微小残留病的潜在标志物。
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, APM 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]. ATPM 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 APM 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 ATPM mutations are stable during disease evolution and closely associated with disease status make it a potential marker for monitoring minimal residual disease.