Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
Korean J Intern Med. 2021 Mar;36(2):413-423. doi: 10.3904/kjim.2019.385. Epub 2020 Oct 23.
BACKGROUND/AIMS: In this study, we tested whether mutations in the methylation pathway genes ten-eleven-translocation 2 (TET2) and DNA methyltransferase gene 3A (DNMT3A) improve the responses of patients with myelodysplastic syndrome (MDS) to decitabine.
We retrospectively sequenced the TET2 and DNMT3A genes from 70 patients diagnosed with de novo MDS between June 2008 and December 2011 and treated with a 5-day regimen of decitabine (290 cycles). We then analyzed treatment outcomes.
Patients with hematological improvement survived longer than those without hematological improvement (22.9 months vs. 10.9 months, p = 0.006). Among the 70 patients, 12 (17.1%) carried TET2 or DNMT3A mutations. The baseline characteristics of patients with wild type or mutated genes were similar. Patients with mutations in TET2 or DNMT3A had a higher overall response rate than those with the wild type genes (82.3% vs. 46.6%, p = 0.023). Multivariate analysis demonstrated that the TET2 or DMNT3A mutation status was associated with improved treatment responses and better overall survival among patients receiving decitabine.
These results demonstrate that TET2 mutations enhance the treatment response of MDS patients to hypomethylating agents like decitabine.
背景/目的：在这项研究中，我们检测了甲基化途径基因 ten-eleven-translocation 2（TET2）和 DNA 甲基转移酶基因 3A（DNMT3A）的突变是否能改善骨髓增生异常综合征（MDS）患者对去甲基化药物地西他滨的反应。
我们回顾性地对 2008 年 6 月至 2011 年 12 月期间诊断为新发 MDS 并接受为期 5 天的地西他滨（290 个周期）治疗的 70 例患者进行了 TET2 和 DNMT3A 基因测序。然后，我们分析了治疗结果。
有血液学改善的患者比没有血液学改善的患者存活时间更长（22.9 个月比 10.9 个月，p=0.006）。在 70 例患者中，有 12 例（17.1%）携带 TET2 或 DNMT3A 突变。基因突变患者与野生型患者的基线特征相似。携带 TET2 或 DNMT3A 突变的患者总反应率高于野生型基因患者（82.3%比 46.6%，p=0.023）。多变量分析表明，TET2 或 DMNT3A 突变状态与地西他滨治疗的反应改善和总生存有关。
这些结果表明，TET2 突变增强了 MDS 患者对地西他滨等低甲基化药物的治疗反应。
