title: Distinct clinical and biological features of de novo acute myeloid leukemia with additional sex comb-like 1 (ASXL1) mutations.
abstract: Mutations in the additional sex comb-like 1 (ASXL1) gene were recently shown in various myeloid malignancies, but they have not been comprehensively investigated in acute myeloid leukemia (AML). In this study, we analyzed ASXL1 mutations in exon 12 in 501 adults with de novo AML. ASXL1 mutations were detected in 54 patients (10.8%), 8.9% among those with normal karyotype and 12.9% among those with abnormal cytogenetics. The mutation was closely associated with older age, male sex, isolated trisomy 8, RUNX1 mutation, and expression of human leukocyte antigen-DR and CD34, but inversely associated with t(15;17), complex cytogenetics, FLT3-internal tandem duplication, NPM1 mutations, WT1 mutations, and expression of CD33 and CD15. Patients with ASXL1 mutations had a shorter overall survival than patients without, but the mutation was not an independent adverse prognostic factor in multivariate analysis. Sequential analyses showed that the original ASXL1 mutations were lost at relapse and/or refractory status in 2 of the 6 relapsed ASXL1-mutated patients studied, whereas 2 of the 109 ASXL1-wild patients acquired a novel ASXL1 mutation at relapse. In conclusion, AML bearing ASXL1 mutations showed distinct clinical and biological features. The ASXL1 mutation status can change during disease evolution in a few patients.
authors.affiliation: Department of Laboratory Medicine, National Taiwan University Hospital, National Taiwan University, Taipei, Taiwan. wchou@ntu.edu.tw
authors.forename: Wen-Chien
authors.initials: WC
authors.lastname: Chou
authors.forename: Huai-Hsuan
authors.initials: HH
authors.lastname: Huang
authors.forename: Hsin-An
authors.initials: HA
authors.lastname: Hou
authors.forename: Chien-Yuan
authors.initials: CY
authors.lastname: Chen
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: Bor-Sheng
authors.initials: BS
authors.lastname: Ko
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: Yen-Ning
authors.initials: YN
authors.lastname: Huang
authors.forename: Yi-Chang
authors.initials: YC
authors.lastname: Chang
authors.forename: Fen-Yu
authors.initials: FY
authors.lastname: Lee
authors.forename: Min-Chih
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: D000328:Adult; D004252:DNA Mutational Analysis; D005091:Exons / Q000235:genetics; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology* / Q000628:therapy; D015999:Multivariate Analysis; D009154:Mutation / Q000235:genetics*; D000090243:Nucleophosmin; D012097:Repressor Proteins / Q000235:genetics*; D016019:Survival Analysis; D016896:Treatment Outcome
chemical_list: C473949:ASXL1 protein, human; C000716967:NPM1 protein, human; D012097:Repressor Proteins; D000090243:Nucleophosmin