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[NPM1 突变的老年急性髓系白血病患者中的共存突变]

[Coexisting mutations in NPM1-mutated elderly adults with acute myeloid leukemia].

作者信息

Qin W, Chao H Y, Cai X H, Lu X Z, Liu J, Wu P, Chen M Y

机构信息

Department of Hematology, Affiliated Changzhou Second Hospital of Nanjing Medical University, Changzhou 213000, China.

Department of Hematotogy, the Second Hospital of Wuxi, Wuxi 214000, China.

出版信息

Zhonghua Yi Xue Za Zhi. 2019 Oct 29;99(40):3152-3157. doi: 10.3760/cma.j.issn.0376-2491.2019.40.006.

Abstract

To explore the coexisting mutations in NPM1 mutated elderly patients with acute myeloid leukemia(AML). 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. 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 0.05) and lower coexistence rate of 4 gene mutations (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 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 0.05) . Patients who carried>4 genes also showed a significantly lower CR rate than those with double gene mutations (0.031). Patients with FLT3-ITD mutations exhibited higher white blood level and lower CR rate than that in nonmutant type group (all 0.05). The CR rate of patients with DNMT3A mutation was also significantly lower than that with nonmutant type (0.033). However, patients with FLT3-TKD mutations showed a higher platelet level than that with nonmutant type (0.019). There was no significant difference in CR rate and peripheral blood cell level between TET2 mutated and nonmutant type. 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.

摘要

探索NPM1突变的老年急性髓系白血病(AML)患者中并存的突变情况。回顾性分析了2013年6月至2018年12月期间常州市第二人民医院和无锡市第二人民医院门诊及住院的152例老年成人(年龄≥60岁)和49例青年成人(年龄18 - 45岁)AML患者的临床资料。使用靶向二代测序(NGS)和桑格测序共检测到51种基因突变。分析并比较了NPM1突变的老年和青年成人AML患者的一般临床特征、并存基因突变的发生情况、并存基因突变与一些临床参数之间的相关性以及初始诱导缓解率。152例老年AML患者中有46例检测到NPM1突变。38例(82.6%)NPM1突变患者同时携带其他基因突变,其中8例(17.4%)单独携带NPM1突变,而14例(30.4%)携带2种突变,16例(34.8%)携带3种突变,8例(17.4%)携带≥4种突变。NPM1突变常与FLT3 - ITD(15例,32.6%)、DNMT3A(10例,21.7%)、TET2(6例,13.4%)和FLT3 - TKD(5例,10.9%)同时出现。与NPM1突变的青年成人相比,老年患者TP53、FLT3 - TKD突变率更高,DNMT3A、RAS突变发生率更低(均P<0.05),4种基因突变并存率更低(P = 0.002)。在老年AML患者中,发现≥4种突变与白细胞水平高于单、双和3种突变并存的患者显著相关(均P<0.05)。随着突变数量的增加,初始诱导后完全缓解(CR)率逐渐降低。携带3种或更多突变的患者CR率低于单基因突变患者(均P<0.05)。携带>4种基因的患者CR率也显著低于双基因突变患者(P = 0.03)。FLT3 - ITD突变患者白细胞水平高于非突变型组,CR率低于非突变型组(均P<0.05)。DNMT3A突变患者的CR率也显著低于非突变型(P = 0.033)。然而,FLT3 - TKD突变患者血小板水平高于非突变型(P = 0.019)。TET2突变型与非突变型患者的CR率和外周血细胞水平无显著差异。NPM1突变的老年AML患者通常存在额外突变,并存突变的数量和类型对老年AML患者的临床特征和CR率有影响。

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