title: DNMT3A mutations in acute myeloid leukemia: stability during disease evolution and clinical implications.
abstract: DNMT3A mutations are associated with poor prognosis in acute myeloid leukemia (AML), but the stability of this mutation during the clinical course remains unclear. In the present study of 500 patients with de novo AML, DNMT3A mutations were identified in 14% of total patients and in 22.9% of AML patients with normal karyotype. DNMT3A mutations were positively associated with older age, higher WBC and platelet counts, intermediate-risk and normal cytogenetics, FLT3 internal tandem duplication, and NPM1, PTPN11, and IDH2 mutations, but were negatively associated with CEBPA mutations. Multivariate analysis demonstrated that the DNMT3A mutation was an independent poor prognostic factor for overall survival and relapse-free survival in total patients and also in normokaryotype group. A scoring system incorporating the DNMT3A mutation and 8 other prognostic factors, including age, WBC count, cytogenetics, and gene mutations, into survival analysis was very useful in stratifying AML patients into different prognostic groups (P < .001). Sequential study of 138 patients during the clinical course showed that DNMT3A mutations were stable during AML evolution. In conclusion, DNMT3A mutations are associated with distinct clinical and biologic features and poor prognosis in de novo AML patients. Furthermore, the DNMT3A mutation may be a potential biomarker for monitoring of minimal residual disease.
authors.affiliation: Division of Hematology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan.
authors.forename: Hsin-An
authors.initials: HA
authors.lastname: Hou
authors.forename: Yuan-Yeh
authors.initials: YY
authors.lastname: Kuo
authors.forename: Chieh-Yu
authors.initials: CY
authors.lastname: Liu
authors.forename: Wen-Chien
authors.initials: WC
authors.lastname: Chou
authors.forename: Ming Cheng
authors.initials: MC
authors.lastname: Lee
authors.forename: Chien-Yuan
authors.initials: CY
authors.lastname: Chen
authors.forename: Liang-In
authors.initials: LI
authors.lastname: Lin
authors.forename: Mei-Hsuan
authors.initials: MH
authors.lastname: Tseng
authors.forename: Chi-Fei
authors.initials: CF
authors.lastname: Huang
authors.forename: Ying-Chieh
authors.initials: YC
authors.lastname: Chiang
authors.forename: Fen-Yu
authors.initials: FY
authors.lastname: Lee
authors.forename: Ming-Chih
authors.initials: MC
authors.lastname: Liu
authors.forename: Chia-Wen
authors.initials: CW
authors.lastname: Liu
authors.forename: Jih-Luh
authors.initials: JL
authors.lastname: Tang
authors.forename: Ming
authors.initials: M
authors.lastname: Yao
authors.forename: Shang-Yi
authors.initials: SY
authors.lastname: Huang
authors.forename: Bor-Sheng
authors.initials: BS
authors.lastname: Ko
authors.forename: Szu-Chun
authors.initials: SC
authors.lastname: Hsu
authors.forename: Shang-Ju
authors.initials: SJ
authors.lastname: Wu
authors.forename: Woei
authors.initials: W
authors.lastname: Tsay
authors.forename: Yao-Chang
authors.initials: YC
authors.lastname: Chen
authors.forename: Hwei-Fang
authors.initials: HF
authors.lastname: Tien
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D002869:Chromosome Aberrations; D004248:DNA (Cytosine-5-)-Methyltransferases / Q000235:genetics*; D000090205:DNA Methyltransferase 3A; D004252:DNA Mutational Analysis; D018450:Disease Progression; D005260:Female; D006801:Humans; D007621:Karyotyping; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy / Q000235:genetics* / Q000401:mortality*; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D000090243:Nucleophosmin; D016133:Polymerase Chain Reaction; D011379:Prognosis; D012074:Remission Induction; D015996:Survival Rate; D055815:Young Adult
chemical_list: C000717967:DNMT3A protein, human; C000716967:NPM1 protein, human; D000090243:Nucleophosmin; D004248:DNA (Cytosine-5-)-Methyltransferases; D000090205:DNA Methyltransferase 3A