title: TP53 mutations in de novo acute myeloid leukemia patients: longitudinal follow-ups show the mutation is stable during disease evolution.
abstract: The TP53 mutation is frequently detected in acute myeloid leukemia (AML) patients with complex karyotype (CK), but the stability of this mutation during the clinical course remains unclear. In this study, TP53 mutations were identified in 7% of 500 patients with de novo AML and 58.8% of patients with CK. TP53 mutations were closely associated with older age, lower white blood cell (WBC) and platelet counts, FAB M6 subtype, unfavorable-risk cytogenetics and CK, but negatively associated with NPM1 mutation, FLT3/ITD and DNMT3A mutation. Multivariate analysis demonstrated that TP53 mutation was an independent poor prognostic factor for overall survival and disease-free survival among the total cohort and the subgroup of patients with CK. A scoring system incorporating TP53 mutation and nine other prognostic factors, including age, WBC counts, cytogenetics and gene mutations, into survival analysis proved to be very useful to stratify AML patients. Sequential study of 420 samples showed that TP53 mutations were stable during AML evolution, whereas the mutation was acquired only in 1 of the 126 TP53 wild-type patients when therapy-related AML originated from different clone emerged. In conclusion, TP53 mutations are associated with distinct clinic-biological features and poor prognosis in de novo AML patients and are rather stable during disease progression.
authors.affiliation: Division of Hematology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan.
authors.forename: H-A
authors.initials: HA
authors.lastname: Hou
authors.affiliation: 1] Division of Hematology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan [2] Department of Laboratory Medicine, National Taiwan University Hospital, Taipei, Taiwan.
authors.forename: W-C
authors.initials: WC
authors.lastname: Chou
authors.affiliation: Graduate Institute of Oncology, College of Medicine, National Taiwan University, Taipei, Taiwan.
authors.forename: Y-Y
authors.initials: YY
authors.lastname: Kuo
authors.affiliation: Biostatistics Consulting Laboratory, Department of Nursing, National Taipei College of Nursing, Taipei, Taiwan.
authors.forename: C-Y
authors.initials: CY
authors.lastname: Liu
authors.affiliation: Department of Clinical Laboratory Sciences and Medical Biotechnology, College of Medicine, National Taiwan University, Taipei, Taiwan.
authors.forename: L-I
authors.initials: LI
authors.lastname: Lin
authors.affiliation: Division of Hematology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan.
authors.forename: M-H
authors.initials: MH
authors.lastname: Tseng
authors.affiliation: Division of Hematology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan.
authors.forename: Y-C
authors.initials: YC
authors.lastname: Chiang
authors.affiliation: Department of Pathology, National Taiwan University Hospital, Taipei, Taiwan.
authors.forename: M-C
authors.initials: MC
authors.lastname: Liu
authors.affiliation: Department of Pathology, National Taiwan University Hospital, Taipei, Taiwan.
authors.forename: C-W
authors.initials: CW
authors.lastname: Liu
authors.affiliation: Division of Hematology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan.
authors.forename: J-L
authors.initials: JL
authors.lastname: Tang
authors.affiliation: Division of Hematology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan.
authors.forename: M
authors.initials: M
authors.lastname: Yao
authors.affiliation: 1] Division of Hematology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan [2] Tai-Chang Stem Cell Therapy Center, National Taiwan University, Taipei, Taiwan.
authors.forename: C-C
authors.initials: CC
authors.lastname: Li
authors.affiliation: Division of Hematology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan.
authors.forename: S-Y
authors.initials: SY
authors.lastname: Huang
authors.affiliation: Division of Hematology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan.
authors.forename: B-S
authors.initials: BS
authors.lastname: Ko
authors.affiliation: Department of Laboratory Medicine, National Taiwan University Hospital, Taipei, Taiwan.
authors.forename: S-C
authors.initials: SC
authors.lastname: Hsu
authors.affiliation: Division of Hematology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan.
authors.forename: C-Y
authors.initials: CY
authors.lastname: Chen
authors.affiliation: 1] Division of Hematology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan [2] Tai-Chang Stem Cell Therapy Center, National Taiwan University, Taipei, Taiwan.
authors.forename: C-T
authors.initials: CT
authors.lastname: Lin
authors.affiliation: Division of Hematology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan.
authors.forename: S-J
authors.initials: SJ
authors.lastname: Wu
authors.affiliation: Division of Hematology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan.
authors.forename: W
authors.initials: W
authors.lastname: Tsay
authors.affiliation: 1] Division of Hematology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan [2] Department of Laboratory Medicine, National Taiwan University Hospital, Taipei, Taiwan.
authors.forename: Y-C
authors.initials: YC
authors.lastname: Chen
authors.affiliation: Division of Hematology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan.
authors.forename: H-F
authors.initials: HF
authors.lastname: Tien
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D053208:Kaplan-Meier Estimate; D015470:Leukemia, Myeloid, Acute / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D009154:Mutation; D000090243:Nucleophosmin; D016016:Proportional Hazards Models; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*; D055815:Young Adult
chemical_list: C000716967:NPM1 protein, human; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; D000090243:Nucleophosmin