title: The prevalence and clinical profiles of FLT3-ITD, FLT3-TKD, NPM1, C-KIT, DNMT3A, and CEBPA mutations in a cohort of patients with de novo acute myeloid leukemia from southwest China.
abstract: While a substantial amount of data on gene mutations related to acute myeloid leukemia (AML) prognosis from western and other populations have been reported, these studies largely describe one or two genes. Additionally, in southwest China, only insufficient data exist regarding FLT3-ITD, FLT3-TKD, NPM1, C-KIT, DNMT3A, and CEBPA mutations have been widely used in clinical settings. Therefore, a comprehensive study about these mutations of clinical importance in the prognosis of AML in western China is necessary. In a cohort of 255 patients with de novo AML, we retrospectively analyzed the prevalence of the six gene mutations, and then we assessed the results in conjunction with clinical characteristics and treatment responses. As for the frequencies of these mutations, the NPM1 mutation occurred most frequently (17.7 %; 42/237), followed by the CEBPA mutation (15.0 %; 19/127) and the FLT3-ITD mutation (10.2 %; 25/244). The frequencies of the FLT3-TKD, DNMT3A, and C-KIT mutations were 3.7 % (9/234), 4.0 % (9/225) and 4.2 % (10/238), respectively. These mutations were closely related to clinical characteristics including FAB classification, gender and age, hemogram, blasts (%), fusion genes, and immunophenotypes. Additionally, a higher complete remission (CR) rate was found in NPM1-mutated patients. The occurrence of these mutations is variable among different countries and regions worldwide, which may provide clues to the etiology of AML. Besides, we identified new clinical characteristics that advance our understanding of these mutations and further clarify the involvement of these mutations in the development of leukemia.
authors.affiliation: Department of Laboratory Medicine, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan Province, People's Republic of China.
authors.forename: Haimei
authors.initials: H
authors.lastname: Gou
authors.affiliation: Department of Laboratory Medicine, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan Province, People's Republic of China.
authors.forename: Juan
authors.initials: J
authors.lastname: Zhou
authors.affiliation: Department of Laboratory Medicine, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan Province, People's Republic of China.
authors.forename: Yuanxin
authors.initials: Y
authors.lastname: Ye
authors.affiliation: Department of Laboratory Medicine, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan Province, People's Republic of China.
authors.forename: Xuejiao
authors.initials: X
authors.lastname: Hu
authors.affiliation: Department of Laboratory Medicine, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan Province, People's Republic of China.
authors.forename: Mengqiao
authors.initials: M
authors.lastname: Shang
authors.affiliation: Department of Laboratory Medicine, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan Province, People's Republic of China.
authors.forename: Jingya
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Laboratory Medicine, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan Province, People's Republic of China.
authors.forename: Zhenzhen
authors.initials: Z
authors.lastname: Zhao
authors.affiliation: Department of Laboratory Medicine, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan Province, People's Republic of China.
authors.forename: Wu
authors.initials: W
authors.lastname: Peng
authors.affiliation: Department of Laboratory Medicine, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan Province, People's Republic of China.
authors.forename: Yanhong
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: Department of Laboratory Medicine, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan Province, People's Republic of China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: Department of Laboratory Medicine, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan Province, People's Republic of China.
authors.forename: Xingbo
authors.initials: X
authors.lastname: Song
authors.affiliation: Department of Laboratory Medicine, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan Province, People's Republic of China. luxiaojun1972@163.com.
authors.forename: Xiaojun
authors.initials: X
authors.lastname: Lu
authors.affiliation: Department of Laboratory Medicine, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan Province, People's Republic of China. bwydoc@163.com.
authors.forename: Binwu
authors.initials: B
authors.lastname: Ying
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D022762:CCAAT-Enhancer-Binding Proteins / Q000235:genetics; D002681:China / Q000453:epidemiology; D003561:Cytarabine / Q000008:administration & dosage; D004248:DNA (Cytosine-5-)-Methyltransferases / Q000235:genetics; D000090205:DNA Methyltransferase 3A; D004252:DNA Mutational Analysis; D003630:Daunorubicin / Q000008:administration & dosage; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006801:Humans; D015255:Idarubicin / Q000008:administration & dosage; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy / Q000453:epidemiology / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009363:Neoplasm Proteins / Q000235:genetics*; D009687:Nuclear Proteins / Q000235:genetics; D000090243:Nucleophosmin; D015514:Oncogene Proteins, Fusion / Q000235:genetics; D019009:Proto-Oncogene Proteins c-kit / Q000235:genetics; D012189:Retrospective Studies; D016896:Treatment Outcome; D055815:Young Adult; D051941:fms-Like Tyrosine Kinase 3 / Q000235:genetics
chemical_list: D022762:CCAAT-Enhancer-Binding Proteins; C515848:CEBPA protein, human; C000717967:DNMT3A protein, human; C000716967:NPM1 protein, human; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D015514:Oncogene Proteins, Fusion; D003561:Cytarabine; D000090243:Nucleophosmin; D004248:DNA (Cytosine-5-)-Methyltransferases; D000090205:DNA Methyltransferase 3A; C497970:FLT3 protein, human; D019009:Proto-Oncogene Proteins c-kit; D051941:fms-Like Tyrosine Kinase 3; D015255:Idarubicin; D003630:Daunorubicin
keywords: Acute myeloid leukemia; Gene; Mutation; Prognosis