Splicing factor mutations predict poor prognosis in patients with de novo acute myeloid leukemia.
Splicing factor mutations predict poor prognosis in patients with de novo acute myeloid leukemia.
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DOI：
10.18632/oncotarget.7000
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发表时间：
2016-02-23
期刊：
影响因子：
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通讯作者：
Tien HF
中科院分区：
文献类型：
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作者：
Hou HA;Liu CY;Kuo YY;Chou WC;Tsai CH;Lin CC;Lin LI;Tseng MH;Chiang YC;Liu MC;Liu CW;Tang JL;Yao M;Li CC;Huang SY;Ko BS;Hsu SC;Chen CY;Lin CT;Wu SJ;Tsay W;Tien HF
剪接因子（SF）基因突变在骨髓增生异常综合征中经常被检测到，但这些基因突变在急性髓系白血病（AML）中的预后相关性仍不清楚。在这项研究中，我们通过 Sanger 测序研究了 500 名新发 AML 患者的三种 SF 基因 SF3B1、U2AF1 和 SRSF2 的突变，并分析了它们的临床相关性。 SF 突变在总队列中的 10.8% 和具有中等风险细胞遗传学的人群中被发现为 13.2%。 SF突变与RUNX1、ASXL1、IDH2和TET2突变密切相关。与无突变的患者相比，SF 突变的 AML 患者的完全缓解率显着较低，无病生存期 (DFS) 和总生存期 (OS) 也较短。多变量分析表明，SF 突变是 DFS 和 OS 的独立不良预后因素。事实证明，结合 SF 突变和其他十个预后因素的评分系统对于对 AML 患者进行风险分层非常有用。配对样本的序贯研究表明，SF 突变在 AML 进化过程中是稳定的。总之，SF 突变与新发 AML 患者的独特临床生物学特征和不良预后相关，并且在疾病进展过程中相当稳定。这些突变可能是新疗法的潜在靶点和用于 AML 疾病监测的生物标志物。
Mutations in splicing factor (SF) genes are frequently detected in myelodysplastic syndrome, but the prognostic relevance of these genes mutations in acute myeloid leukemia (AML) remains unclear. In this study, we investigated mutations of three SF genes, SF3B1, U2AF1 and SRSF2, by Sanger sequencing in 500 patients with de novo AML and analysed their clinical relevance. SF mutations were identified in 10.8% of total cohort and 13.2% of those with intermediate-risk cytogenetics. SF mutations were closely associated with RUNX1, ASXL1, IDH2 and TET2 mutations. SF-mutated AML patients had a significantly lower complete remission rate and shorter disease-free survival (DFS) and overall survival (OS) than those without the mutation. Multivariate analysis demonstrated that SFmutation was an independent poor prognostic factor for DFS and OS. A scoring system incorporating SF mutation and ten other prognostic factors was proved very useful to risk-stratify AML patients. Sequential study of paired samples showed that SF mutations were stable during AML evolution. In conclusion, SF mutations are associated with distinct clinic-biological features and poor prognosis in de novo AML patients and are rather stable during disease progression. These mutations may be potential targets for novel treatment and biomarkers for disease monitoring in AML.