title: A targeted next-generation sequencing in the molecular risk stratification of adult acute myeloid leukemia: implications for clinical practice.
abstract: Conventional cytogenetics can categorize patients with acute myeloid leukemia (AML) into favorable, intermediate, and unfavorable-risk groups; however, patients with intermediate-risk cytogenetics represent the major population with variable outcomes. Because molecular profiling can assist with AML prognosis and next-generation sequencing allows simultaneous sequencing of many target genes, we analyzed 260 genes in 112 patients with de novo AML who received standard treatment. Multivariate analysis showed that karyotypes and mutation status of TET2, PHF6, KIT, and NPM1mutation/FLT3- internal tandem duplication (ITD)negativewere independent prognostic factors for the entire cohort. Among patients with intermediate-risk cytogenetics, patients with mutations in CEBPAdouble mutation, IDH2, and NPM1 in the absence of FLT3-ITD were associated with improved Overall survival (OS), similar to those with favorable-risk cytogenetics; patients with mutations in TET2, RUNX1, ASXL1, and DNMT3A were associated with reduced OS, similar to those with unfavorable-risk cytogenetics. We concluded that integration of cytogenetic and molecular profiling improves prognostic stratification of patients into three groups with more distinct prognoses (P < 0.001) and significantly reduces the number of patients classified as intermediate risk. In addition, our study demonstrates that next-generation sequencing (NGS)-based multi-gene sequencing is clinically applicable in establishing an accurate risk stratification system for guiding therapeutic decisions.
authors.affiliation: Department of Medical Genetics, National Taiwan University Hospital, Taipei, Taiwan.|Graduate Institute of Clinical Medicine, China Medical University, Taichung, Taiwan.
authors.forename: Po-Han
authors.initials: PH
authors.lastname: Lin
authors.affiliation: Department of Medical Genetics, National Taiwan University Hospital, Taipei, Taiwan.
authors.forename: Huei-Ying
authors.initials: HY
authors.lastname: Li
authors.affiliation: Department of Medical Genetics, National Taiwan University Hospital, Taipei, Taiwan.
authors.forename: Sheng-Chih
authors.initials: SC
authors.lastname: Fan
authors.affiliation: Department of Medical Genetics, National Taiwan University Hospital, Taipei, Taiwan.
authors.forename: Tzu-Hang
authors.initials: TH
authors.lastname: Yuan
authors.affiliation: Department of Medical Genetics, National Taiwan University Hospital, Taipei, Taiwan.|Department of Genomic Medicine, Center for Medical Genetics, Changhua Christian Hospital, Changhua, Taiwan.
authors.forename: Ming
authors.initials: M
authors.lastname: Chen
authors.affiliation: Department of Medical Genetics, National Taiwan University Hospital, Taipei, Taiwan.
authors.forename: Yu-Hua
authors.initials: YH
authors.lastname: Hsu
authors.affiliation: Department of Medical Genetics, National Taiwan University Hospital, Taipei, Taiwan.
authors.forename: Yu-Hsuan
authors.initials: YH
authors.lastname: Yang
authors.affiliation: Department of Life Sciences, National Chung Hsing University, Taichung, 40227, Taiwan.
authors.forename: Long-Yuan
authors.initials: LY
authors.lastname: Li
authors.affiliation: Division of Hematology and Oncology, Department of Internal Medicine, China Medical University Hospital.|Department of Internal Medicine, Graduate Institute of Clinical Medicine, China Medical University, Taichung, Taiwan.
authors.forename: Su-Peng
authors.initials: SP
authors.lastname: Yeh
authors.affiliation: Division of Hematology and Oncology, Department of Internal Medicine, China Medical University Hospital.|Department of Internal Medicine, Graduate Institute of Clinical Medicine, China Medical University, Taichung, Taiwan.
authors.forename: Li-Yuan
authors.initials: LY
authors.lastname: Bai
authors.affiliation: Division of Hematology and Oncology, Department of Internal Medicine, China Medical University Hospital.
authors.forename: Yu-Min
authors.initials: YM
authors.lastname: Liao
authors.affiliation: Division of Hematology and Oncology, Department of Internal Medicine, China Medical University Hospital.
authors.forename: Chen-Yuan
authors.initials: CY
authors.lastname: Lin
authors.affiliation: Division of Hematology and Oncology, Department of Internal Medicine, China Medical University Hospital.
authors.forename: Ching-Yun
authors.initials: CY
authors.lastname: Hsieh
authors.affiliation: Division of Hematology and Oncology, Department of Internal Medicine, China Medical University Hospital.
authors.forename: Ching-Chan
authors.initials: CC
authors.lastname: Lin
authors.affiliation: Division of Hematology and Oncology, Department of Internal Medicine, China Medical University Hospital.
authors.forename: Che-Hung
authors.initials: CH
authors.lastname: Lin
authors.affiliation: Division of Hematology and Oncology, Department of Internal Medicine, China Medical University Hospital.
authors.forename: Ming-Yu
authors.initials: MY
authors.lastname: Lien
authors.affiliation: Division of Hematology and Oncology, Department of Internal Medicine, China Medical University Hospital.
authors.forename: Tzu-Ting
authors.initials: TT
authors.lastname: Chen
authors.affiliation: Department of Medical Genetics, National Taiwan University Hospital, Taipei, Taiwan.|Department of Pediatrics, National Taiwan University Hospital, Taipei, Taiwan.
authors.forename: Yen-Hsuan
authors.initials: YH
authors.lastname: Ni
authors.affiliation: Division of Hematology and Oncology, Department of Internal Medicine, China Medical University Hospital.|Department of Internal Medicine, Graduate Institute of Clinical Medicine, China Medical University, Taichung, Taiwan.
authors.forename: Chang-Fang
authors.initials: CF
authors.lastname: Chiu
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D002648:Child; D020732:Cytogenetic Analysis; D005260:Female; D053263:Gene Regulatory Networks; D020022:Genetic Predisposition to Disease; D059014:High-Throughput Nucleotide Sequencing / Q000379:methods*; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D000090243:Nucleophosmin; D011379:Prognosis; D017422:Sequence Analysis, DNA / Q000379:methods*; D016019:Survival Analysis; D055815:Young Adult
keywords: Acute myeloid leukemia; gene mutations; next-generation sequencing; precision medicine; prognosis