A targeted next-generation sequencing in the molecular risk stratification of adult acute myeloid leukemia: implications for clinical practice.
A targeted next-generation sequencing in the molecular risk stratification of adult acute myeloid leukemia: implications for clinical practice.
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DOI：
10.1002/cam4.969
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发表时间：
2017-02
期刊：
影响因子：
4
通讯作者：
Chiu CF
中科院分区：
文献类型：
--
作者：
Lin PH;Li HY;Fan SC;Yuan TH;Chen M;Hsu YH;Yang YH;Li LY;Yeh SP;Bai LY;Liao YM;Lin CY;Hsieh CY;Lin CC;Lin CH;Lien MY;Chen TT;Ni YH;Chiu CF
传统的细胞遗传学可以将急性髓性白血病（AML）患者分为有利、中等和不利风险组；然而，具有中等风险细胞遗传学的患者代表了具有可变结果的主要人群。由于分子谱分析有助于AML预后，下一代测序允许同时测序许多靶基因，我们分析了112例接受标准治疗的新发AML患者的260个基因。多因素分析显示，TET2、PHF6、KIT和NPM1突变/FLT3 -内部串联重复（ITD）阴性的核型和突变状态是整个队列的独立预后因素。在中等风险细胞遗传学患者中，在没有FLT3 - ITD的情况下，CEBPA双突变、IDH2和NPM1突变的患者与有利风险细胞遗传学患者的总生存期（OS）改善相关；TET2、RUNX1、ASXL1和DNMT3A基因突变的患者与不良风险细胞遗传学患者的OS降低相关。我们的结论是，细胞遗传学和分子谱的整合改善了患者的预后分层，将患者分为预后更明显的三组（P < 0.001），并显著减少了分类为中间风险的患者数量。此外，我们的研究表明，基于下一代测序（NGS）的多基因测序在临床上可用于建立准确的风险分层系统，以指导治疗决策。
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.