Open AccessA targeted next‐generation sequencing in the molecular risk stratification of adult acute myeloid leukemia: implications for clinical practice
Author(s) -
Lin PoHan,
Li HueiYing,
Fan ShengChih,
Yuan TzuHang,
Chen Ming,
Hsu YuHua,
Yang YuHsuan,
Li LongYuan,
Yeh SuPeng,
Bai LiYuan,
Liao YuMin,
Lin ChenYuan,
Hsieh ChingYun,
Lin ChingChan,
Lin CheHung,
Lien MingYu,
Chen TzuTing,
Ni YenHsuan,
Chiu ChangFang
Publication year - 2017
Publication title -
cancer medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.403
H-Index - 53
ISSN - 2045-7634
DOI - 10.1002/cam4.969
Subject(s) - cebpa , cytogenetics , myeloid leukemia , npm1 , oncology , medicine , biology , karyotype , gene , mutation , genetics , chromosome
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 TET 2 , PHF 6 , KIT , and NPM 1 mutation / FLT 3 ‐ 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 , IDH 2 , and NPM 1 in the absence of FLT 3 ‐ ITD were associated with improved Overall survival ( OS ), similar to those with favorable‐risk cytogenetics; patients with mutations in TET 2 , RUNX 1 , ASXL 1 , and DNMT 3A 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.