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標題: A targeted next-generation sequencing in the molecular risk stratification of adult acute myeloid leukemia: implications for clinical practice
作者: Lin, Po-Han
Li, Huei-Ying
Fan, Sheng-Chih
Yuan, Tzu-Hang
Chen, Ming
Hsu, Yu-Hua
Yang, Yu-Hsuan
Li, Long-Yuan
Yeh, Su-Peng
Bai, Li-Yuan
Liao, Yu-Min
Lin, Chen-Yuan
Hsieh, Ching-Yun
Lin, Ching-Chan
Lin, Che-Hung
Lien, Ming-Yu
Chen, Tzu-Ting
Ni, Yen-Hsuan
Chiu, Chang-Fang
關鍵字: Acute myeloid leukemia;gene mutations;next-generation sequencing;precision medicine;prognosis;Adolescent;Adult;Aged;Child;Cytogenetic Analysis;Female;Gene Regulatory Networks;High-Throughput Nucleotide Sequencing;Humans;Leukemia, Myeloid, Acute;Male;Middle Aged;Prognosis;Sequence Analysis, DNA;Survival Analysis;Young Adult;Genetic Predisposition to Disease;Mutation
Project: Cancer medicine, Volume 6, Issue 2, Page(s) 349-360.
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)negative were 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.
DOI: 10.1002/cam4.969
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