• Po-Han Lin, Huei-Ying Li, Sheng-Chih Fan, Tzu-Hang Yuan, Ming Chen, Yu-Hua Hsu, Yu-Hsuan Yang, Long-Yuan Li, Su-Peng Yeh, Li-Yuan Bai, Yu-Min Liao, Chen-Yuan Lin, Ching-Yun Hsieh, Ching-Chan Lin, Che-Hung Lin, Ming-Yu Lien, Tzu-Ting Chen, Yen-Hsuan Ni, and Chang-Fang Chiu.
• Department of Medical Genetics, National Taiwan University Hospital, Taipei, Taiwan.
• Cancer Med. 2017 Feb 1; 6 (2): 349-360.

AbstractConventional 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.© 2017 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

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