伴PTPN11基因突变的成人急性髓系白血病患者的临床特征分析  

Characteristic Analysis of Adult Acute Myeloid Leukemia Patients with PTPN11 Gene Mutation

作　　者：盛丽 刘亚姣 周竞奋 晁红颖[3] 华海应 周新[4] 赵晓红[5] SHENG Li;LIU Ya-Jiao;ZHOU Jing-Fen;CHAO Hong-Ying;HUA Hai-Ying;ZHOU Xin;ZHAO Xiao-Hong(Deparment of Hematology,The Affiliated Hospial of Jiangnan University,Wiai 214122,Jiangsu Province,China;Wiai School of Medicine,Jiangnaon University,Wixi 214122,Jiangsu Province,China;Department of Hematology,Changzhou Second People's Hospital,Changzhou 213003,Jiangsu Province,China;Department of Hematology,Wixi People’s Hospital,Wiuxri 214023,Jiangsu Province,China;S Department of Hematology,Wixi Second People s Hospial,Wuxi 214001,Jiangsu Province,China)

机构地区：[1]江南大学附属医院血液科,江苏无锡214122 [2]江南大学无锡医学院,江苏无锡214122 [3]常州市第二人民医院血液科,江苏常州213003 [4]无锡市人民医院血液科,江苏无锡214023 [5]无锡市第二人民医院血液科,江苏无锡214001

出　　处：《中国实验血液学杂志》2024年第4期1063-1070,共8页Journal of Experimental Hematology

摘　　要：目的:探讨成人急性髓系白血病(AML)患者PTPN11基因突变及其伴随基因突变的发生情况及临床特征。方法:应用二代测序技术联合Sanger测序,回顾性分析从2017年1月至2022年7月由江南大学附属医院、常州市第二人民医院、无锡市人民医院以及无锡市第二人民医院收治的初诊成人AML患者51种基因突变,采用多重PCR检测41种常见白血病融合基因。结果:451例初诊成人AML中,共检测出34例患者携带PTPN11基因突变,突变率为7.5%。34例患者中,检测出37个PTPN11突变位点,其受N-SH2(31例)和PTP(6例)结构域内的错义突变影响,且大部分聚集在第3外显子(31例)。伴有PTPN11突变患者的血小板计数为76.5(23.5,119.0)×10^(9)/L,高于野生型患者的41.0(22.0,82.5)×10^(9)/L(P<0.05),而两组性别、年龄、外周血白细胞计数、血红蛋白水平及骨髓原始细胞比例差异均无统计学意义(P>0.05)。PTPN11突变主要表现为M5亚型,其次为M2及M4亚型,较少发生于M3及M6亚型。PTPN11突变型及野生型患者的FAB亚型分布差异无统计学意义(P>0.05)。共有118例AML患者检测到融合基因阳性,其中,伴有PTPN11突变患者的MLL-AF6阳性发生率高于野生型患者(P<0.01)。34例PTPN11基因突变中有97.1%同时伴随其他基因突变,最常见的由高到低依次为NPM1(38.2%)、NRAS(32.4%)、FLT3-ITD(32.4%)、DNMT3A(32.4%)、KRAS(23.5%)等。结论:PTPN11基因突变在AML患者中有一定的发生率,多见于第3号外显子,且均为错义突变。该基因突变多与NPM1基因突变同时存在,FAB分型多表现为M5亚型,具有更高的血小板水平。Objective:To investigate the incidence of PTPN11 gene mutation and its associated gene mutations in adult patients with acute myeloid leukemia(AML),and analyze its clinical characteristics.Methods:Second-generation sequencing and Sanger sequencing were used to detect 51 gene mutations,and multiplex-PCR was used to detect 41 fusion genes from 451 newly diagnosed adult AML patients admitted to Affiliated Hospital of Jiangnan University,Changzhou Second People's Hospital,Wuxi People's Hospital and Wuxi Second People's Hospital from January 2017 to July 2022.Results:Among 451 primary adult AML patients,the PTPN11 gene mutation was detected in 34 cases,and the mutation rate was 7.5%.In the 34 patients,37 PTPN11 alterations were found,which were exclusively missense mutations affecting residues located within the N-SH2(31 cases)and PTP(6 cases)domains and clustered overwhelmingly in exon 3.The platelet count of PTPN11 mutation patients was 76.5(23.5,119.0)×10^(9)/L,which was significantly higher than 41.0(22.0,82.5)×10^(9)/L of wild-type patients(P<0.05).While,there were no significant differences in sex,age,peripheral white blood cell count,hemoglobin,and bone marrow blast between PTPN11 mutation and wild-type patients(P>0.05).In FAB subtypes,PTPN11 mutations were mainly distributed in M5,followed by M2and M4,less frequently in M3and M6.There was no significant difference in the distribution of FAB subtypes between PTPN11 mutation and wild-type patients(P>0.05).A total of118AML patients were detected positive fusion gene,among which patients with PTPN11 mutations had a higher incidence of positive MLL-AF6than wild-type ones(P<0.01).97.1%of34patients with PTPN11 mutations were accompanied by other mutations,in descending order,they were respectively NPM1(38.2%),NRAS(32.4%),FLT3-ITD(32.4%),DNMT3A(32.4%)and KRAS(23.5%),etc.Conclusion:PTPN11 mutation has a certain incidence in AML patients and is clustered overwhelmingly in exon3.ALL of them are exclusively missense mutations,and most often present in conjunction with N

关 键 词：急性髓系白血病 PTPN11 基因突变 临床特征 

分 类 号：R733.71[医药卫生—肿瘤]