Ruan Min, Zhang Li, Han Cong, Liu Xiaoming, Ai Xiaofei, Zhang Jiayuan, Liu Tianfeng, Yang Wenyu, Chen Xiaojuan, Guo Ye, Wang Shuchun, Li Qinghua, Zou Yao, Chen Yumei, Zhu Xiaofan
Department of Pediatrics and Pathological Diagnosis Center, Institute of Hematology and Blood Disease Hospital, Chinese Academy of Medical Sciences, Tianjin 300020, China.
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Zhonghua Er Ke Za Zhi. 2014 Apr;52(4):303-7.
To evaluate the frequency of the nucleophosmin (NPM1) gene and the CCAAT/enhancer binding protein α gene (CEBPA) through polymerase chain reaction (PCR) array in pediatric patients with cytogenetically normal acute myeloid leukemia (CN-AML) and explore the clinical significances of these mutations.
Between August 2009 and December 2012, 30 children (<16 years old) with newly diagnosed CN-AML were included. The clinical characteristics were analyzed in these patients. PCR combined with direct sequencing was used to detect NPM1, CEBPA gene mutations. All the data were statistically analyzed using SPSS17.0 software.
The gene mutations were detected in each of the 30 patients. NPM1 mutation was positive in three patients (10%) with type A mutation, while CEBPA mutation was positive in two patients (6.7%) with double mutations (TAD, bZIP) . Besides, FLT3/ITD mutation was positive in three patients. Patients with NPM1 or FLT3/ITD had a significantly elevated diagnostic WBC count with a median diagnostic WBC count of 102.80×10(9)/L compared with 18.56×10(9)/L for the patients without mutations(t = 2.353, P = 0.043), as well as the marrow blast percentage (94.0% vs. 80.0%, t = 3.804, P = 0.002). The complete remission was achieved in all the 3 patients with NPM1 mutations and 2 patients with CEBPA mutations. All the patients with these mutations also achieved 2-year event-free survival (EFS) and 2-year overall survival (OS), while 2-year EFS and 2-year OS of the other patients were (40.1 ± 11.2)% and (51.8 ± 10.9)% (P = 0.044, 0.091, respectively).
NPM1 and CEBPA mutations may indicate a favorable prognosis in pediatric CN-AML.
通过聚合酶链反应（PCR）芯片评估细胞遗传学正常的急性髓系白血病（CN-AML）患儿中核磷蛋白（NPM1）基因和CCAAT/增强子结合蛋白α基因（CEBPA）的突变频率，并探讨这些突变的临床意义。
纳入2009年8月至2012年12月期间新诊断的30例年龄小于16岁的CN-AML患儿。分析这些患者的临床特征。采用PCR结合直接测序法检测NPM1、CEBPA基因突变。所有数据均使用SPSS17.0软件进行统计学分析。
30例患者均检测到基因突变。3例患者（10%）NPM1突变呈阳性，为A型突变；2例患者（6.7%）CEBPA突变呈阳性，为双突变（TAD、bZIP）。此外，3例患者FLT3/ITD突变呈阳性。与未发生突变的患者相比，发生NPM1或FLT3/ITD突变的患者诊断时白细胞计数显著升高，诊断时白细胞计数中位数为102.80×10⁹/L，而未发生突变的患者为18.56×10⁹/L（t = 2.353，P = 0.043），骨髓原始细胞百分比也较高（94.0%对80.0%，t = 3.804，P = 0.002）。3例NPM1突变患者和2例CEBPA突变患者均实现完全缓解。所有发生这些突变的患者也均实现了2年无事件生存（EFS）和2年总生存（OS），而其他患者的2年EFS和2年OS分别为（40.1±11.2）%和（51.8±10.9）%（P分别为0.044、0.091）。
NPM1和CEBPA突变可能提示儿童CN-AML预后良好。
