title: Genetic alterations and their clinical implications in older patients with acute myeloid leukemia.
abstract: A number of patient-specific and leukemia-associated factors are related to the poor outcome in older patients with acute myeloid leukemia (AML). However, comprehensive studies regarding the impact of genetic alterations in this group of patients are limited. In this study, we compared relevant mutations in 21 genes between AML patients aged 60 years or older and those younger and exposed their prognostic implications. Compared with the younger patients, the elderly had significantly higher incidences of PTPN11, NPM1, RUNX1, ASXL1, TET2, DNMT3A and TP53 mutations but a lower frequency of WT1 mutations. The older patients more frequently harbored one or more adverse genetic alterations. Multivariate analysis showed that DNMT3A and TP53 mutations were independent poor prognostic factors among the elderly, while NPM1 mutation in the absence of FLT3/ITD was an independent favorable prognostic factor. Furthermore, the status of mutations could well stratify older patients with intermediate-risk cytogenetics into three risk groups. In conclusion, older AML patients showed distinct genetic alterations from the younger group. Integration of cytogenetics and molecular mutations can better risk-stratify older AML patients. Development of novel therapies is needed to improve the outcome of older patients with poor prognosis under current treatment modalities.
authors.affiliation: Division of Hematology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan.|Graduate Institute of Clinical Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan.|Tai-Cheng Stem Cell Therapy Center, National Taiwan University, Taipei, Taiwan.
authors.forename: C-H
authors.initials: CH
authors.lastname: Tsai
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: Division of Hematology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan.|Tai-Cheng Stem Cell Therapy Center, National Taiwan University, Taipei, Taiwan.
authors.forename: J-L
authors.initials: JL
authors.lastname: Tang
authors.affiliation: Biostatistics Consulting Laboratory, School of Nursing, National Taipei University of Nursing and Health Sciences, Taipei, Taiwan.
authors.forename: C-Y
authors.initials: CY
authors.lastname: Liu
authors.affiliation: Division of Hematology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan.|Graduate Institute of Clinical Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan.|Department of Laboratory Medicine, National Taiwan University Hospital, Taipei, Taiwan.
authors.forename: C-C
authors.initials: CC
authors.lastname: Lin
authors.affiliation: Division of Hematology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan.|Department of Laboratory Medicine, National Taiwan University Hospital, Taipei, Taiwan.
authors.forename: W-C
authors.initials: WC
authors.lastname: Chou
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: Graduate Institute of Oncology, College of Medicine, National Taiwan University, Taipei, Taiwan.
authors.forename: Y-Y
authors.initials: YY
authors.lastname: Kuo
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: 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: W
authors.initials: W
authors.lastname: Tsay
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: Division of Hematology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan.|Tai-Cheng 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: Division of Hematology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan.|Tai-Cheng 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: H-F
authors.initials: HF
authors.lastname: Tien
mesh_terms: D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D003582:Cytogenetics; D004248:DNA (Cytosine-5-)-Methyltransferases / Q000235:genetics; D000090205:DNA Methyltransferase 3A; D005260:Female; D016158:Genes, p53 / Q000235:genetics; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000175:diagnosis / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009154:Mutation; D009687:Nuclear Proteins / Q000235:genetics; D000090243:Nucleophosmin; D011379:Prognosis; D018570:Risk Assessment; D051941:fms-Like Tyrosine Kinase 3 / Q000235:genetics
chemical_list: C000717967:DNMT3A protein, human; C000716967:NPM1 protein, human; D009687:Nuclear Proteins; D000090243:Nucleophosmin; D004248:DNA (Cytosine-5-)-Methyltransferases; D000090205:DNA Methyltransferase 3A; C497970:FLT3 protein, human; D051941:fms-Like Tyrosine Kinase 3