Objective: To explore the coexisting mutations in NPM1 mutated elderly patients with acute myeloid leukemia(AML). Methods: The clinical data of 152 elderly adults(aged≥60 years) and 49 young adults(aged 18-45 years) with AML between June 2013 and December 2018 in outpatient and hospitalized patients of Changzhou Second People's Hospital and Wuxi Second People's Hospital were retrospectively analyzed. A total of 51 gene mutations were detected using targeted next-generation sequencing (NGS) and sanger sequencing. The general clinical characteristics, the occurrence of coexistence gene mutations, the correlation between coexistence gene mutations and some clinical parameters, and the initial induction remission rate between elderly and young adult AML patients with NPM1 mutations were analyzed and compared. Results: NPM1 mutations were detected in 46 of 152 elderly AML patients. Thirty eight patients (82.6%) with NPM1 mutations carried other gene mutations at the same time, among whom 8 patients (17.4%) carried NPM1 mutations alone, while 14(30.4%) carried 2, 16 (34.8%) carried 3, and 8 (17.4%) carried ≥ 4 mutations. NPM1 mutations frequently co-occurred with FLT3-ITD15 cases (32.6%) , DNMT3A10 (21.7%) , TET26 (13.4%) and FLT3-TKD5 (10.9%) . Compared with young adults with NPM1 mutations, elderly patients had higher TP53, FLT3-TKD rates, lower incidence of DNMT3A, RAS mutation (all P<0.05) and lower coexistence rate of 4 gene mutations (P=0.002).The presence of ≥ 4 mutations was found to be significantly associated with higher white blood level than those in patients with single, double and 3 mutations coexisted in elderly adults AML patients(all P<0.05). With the increase of the amount of mutations, the complete remission(CR) rate decreased gradually after the initial induction. Patients who carried 3 or more mutations showed a lower CR rate than those with single gene mutations (all P<0.05) . Patients who carried>4 genes also showed a significantly lower CR rate than those with double gene mutations (P=0.031). Patients with FLT3-ITD mutations exhibited higher white blood level and lower CR rate than that in nonmutant type group (all P<0.05). The CR rate of patients with DNMT3A mutation was also significantly lower than that with nonmutant type (P=0.033). However, patients with FLT3-TKD mutations showed a higher platelet level than that with nonmutant type (P=0.019). There was no significant difference in CR rate and peripheral blood cell level between TET2 mutated and nonmutant type. Conclusion: NPM1 mutated elderly patients with AML commonly show additional mutations, and the amount and type of coexisting mutations have an influence on the clinical features and CR rate of elderly patients with AML.
目的： 探讨伴核仁磷酸蛋白1（NPM1）突变的老年急性髓系白血病（AML）患者中共存基因突变发生情况。 方法： 回顾性分析常州市第二人民医院及无锡市第二人民医院2013年6月至2018年12月门诊及住院治疗的年龄≥60岁原发AML患者152例（老年组）及年龄18~45岁的患者49例（年轻成人组），采用高通量DNA测序技术联合Sanger测序法检测51种基因突变。分析比较NPM1突变的老年组与年轻成人组患者的一般临床特点、共存基因突变发生情况、共存基因突变、野生型与部分临床参数间及初次诱导缓解率间的相关性分析。 结果： 老年组152例患者中共检出46例携带NPM1突变，38例（82.6%）NPM1突变患者同时携带其他基因突变。其中，NPM1单独突变8例（17.4%）、双基因突变14例（30.4%）、3种基因突变16例（34.8%）、≥4种基因突变共存8例（17.4%）；突变类型为：FLT3-ITD15例（32.6%）、DNMT3A10例（21.7%）、TET26例（13.4%）、FLT3-TKD5例（10.9%）等。与年轻成人组NPM1突变相比，老年组具有更高的TP53、FLT3-TKD，更低的DNMT3A、RAS突变发生率（均P<0.05）及更低的4种基因突变共存率（P=0.002）。老年组中，≥4种基因突变患者的白细胞（WBC）水平明显高于单基因突变、双基因突变及3种基因突变共存者（均P<0.05）；随着基因突变数目增加，初次诱导治疗后完全缓解（CR）率下降，3基因突变及≥4种基因共存患者的均明显低于单基因突变（均P<0.05）；≥4种基因共存患者的CR率明显亦低于双基因突变者（P=0.031）。与FLT3-ITD非突变型相比，共存基因突变为FLT3-ITD者具有更高的外周WBC水平（P=0.018）及更低的CR率（P=0.001），伴DNMT3A患者具有更低的CR率（P=0.033）；伴FLT3-TKD突变患者较非突变型具有更高的外周血小板水平（P=0.019）。 结论： NPM1突变阳性的老年AML患者常携带额外基因突变，NPM1突变共存的基因突变个数及突变类型对患者的临床特征及CR率有一定影响。.
Keywords: Gene; Leukemia, myeloid, acute; Mutation.