title: TET2 mutation is an unfavorable prognostic factor in acute myeloid leukemia patients with intermediate-risk cytogenetics.
abstract: The studies concerning clinical implications of TET2 mutation in patients with primary acute myeloid leukemia (AML) are scarce. We analyzed TET2 mutation in 486 adult patients with primary AML. TET2 mutation occurred in 13.2% of our patients and was closely associated with older age, higher white blood cell and blast counts, lower platelet numbers, normal karyotype, intermediate-risk cytogenetics, isolated trisomy 8, NPM1 mutation, and ASXL1 mutation but mutually exclusive with IDH mutation. TET2 mutation is an unfavorable prognostic factor in patients with intermediate-risk cytogenetics, and its negative impact was further enhanced when the mutation was combined with FLT3-ITD, NPM1-wild, or unfavorable genotypes (other than NPM1(+)/FLT3-ITD(-) or CEBPA(+)). A scoring system integrating TET2 mutation with FLT3-ITD, NPM1, and CEBPA mutations could well separate AML patients with intermediate-risk cytogenetics into 4 groups with different prognoses (P < .0001). Sequential analysis revealed that TET2 mutation detected at diagnosis was frequently lost at relapse; rarely, the mutation was acquired at relapse in those without TET2 mutation at diagnosis. In conclusion, TET2 mutation is associated with poor prognosis in AML patients with intermediate-risk cytogenetics, especially when it is combined with other adverse molecular markers. TET2 mutation appeared to be unstable during disease evolution.
authors.affiliation: Department of Laboratory Medicine, National Taiwan University Hospital, Taipei, Taiwan.
authors.forename: Wen-Chien
authors.initials: WC
authors.lastname: Chou
authors.forename: Sheng-Chieh
authors.initials: SC
authors.lastname: Chou
authors.forename: Chieh-Yu
authors.initials: CY
authors.lastname: Liu
authors.forename: Chien-Yuan
authors.initials: CY
authors.lastname: Chen
authors.forename: Hsin-An
authors.initials: HA
authors.lastname: Hou
authors.forename: Yuan-Yeh
authors.initials: YY
authors.lastname: Kuo
authors.forename: Ming-Cheng
authors.initials: MC
authors.lastname: Lee
authors.forename: Bor-Sheng
authors.initials: BS
authors.lastname: Ko
authors.forename: Jih-Luh
authors.initials: JL
authors.lastname: Tang
authors.forename: Ming
authors.initials: M
authors.lastname: Yao
authors.forename: Woei
authors.initials: W
authors.lastname: Tsay
authors.forename: Shang-Ju
authors.initials: SJ
authors.lastname: Wu
authors.forename: Shang-Yi
authors.initials: SY
authors.lastname: Huang
authors.forename: Szu-Chun
authors.initials: SC
authors.lastname: Hsu
authors.forename: Yao-Chang
authors.initials: YC
authors.lastname: Chen
authors.forename: Yi-Chang
authors.initials: YC
authors.lastname: Chang
authors.forename: Yi-Yi
authors.initials: YY
authors.lastname: Kuo
authors.forename: Kuan-Ting
authors.initials: KT
authors.lastname: Kuo
authors.forename: Fen-Yu
authors.initials: FY
authors.lastname: Lee
authors.forename: Ming-Chi
authors.initials: MC
authors.lastname: Liu
authors.forename: Chia-Wen
authors.initials: CW
authors.lastname: Liu
authors.forename: Mei-Hsuan
authors.initials: MH
authors.lastname: Tseng
authors.forename: Chi-Fei
authors.initials: CF
authors.lastname: Huang
authors.forename: Hwei-Fang
authors.initials: HF
authors.lastname: Tien
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D020732:Cytogenetic Analysis; D004268:DNA-Binding Proteins / Q000235:genetics*; D049308:Dioxygenases; D005260:Female; D006801:Humans; D007621:Karyotyping; D015470:Leukemia, Myeloid, Acute / Q000175:diagnosis* / Q000235:genetics*; D008297:Male; D009154:Mutation; D000090243:Nucleophosmin; D011379:Prognosis; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D016019:Survival Analysis; D055815:Young Adult
chemical_list: D004268:DNA-Binding Proteins; C000716967:NPM1 protein, human; D011518:Proto-Oncogene Proteins; D000090243:Nucleophosmin; D049308:Dioxygenases; C541081:TET2 protein, human