A targeted next‐generation sequencing in the molecular risk stratification of adult acute myeloid leukemia: implications for clinical practice. (10th January 2017)

• Record Type: Journal Article
• Authors: 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
• Is Part Of: Cancer medicine. Volume 6:Number 2(2017:Feb.)
• Page Start: 349
• Page End: 360
• Publication Date: 2017-01-10
• Subjects: Acute myeloid leukemia -- gene mutations -- next‐generation sequencing -- precision medicine -- prognosis; 616.994005
• DOI: 10.1002/cam4.969
• Languages: English
• ISSNs: 2045-7634

Abstract

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 NPM1 mutation / FLT3 ‐ internal tandem duplication (ITD) negative were independent prognostic factors for the entire cohort. Among patients with intermediate‐risk cytogenetics, patients with mutations in CEBPA double 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. Abstract : We comprehensively analyzed 260 genes by next‐generation sequencing (NGS) in 112 patients with de novo acute myeloid leukemia (AML). Our result suggested that parallel sequencing using NGS was a good strategy to handle the testing of multiple genes and could provide a rapid and accurate risk classification system for the clinical management of AML patients.