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TET2缺陷在骨髓增生异常综合征中的预后作用:一项荟萃分析。

Prognostic role of TET2 deficiency in myelodysplastic syndromes: A meta-analysis.

作者信息

Lin Yun, Lin Zhijuan, Cheng Kun, Fang Zhihong, Li Zhifeng, Luo Yiming, Xu Bing

机构信息

Department of Hematology, The First Affiliated Hospital of Xiamen University, Xiamen, P.R. China.

Thoracic Department, People's Hospital Affiliated to Fujian University of Traditional Chinese Medicine, Fuzhou, P.R. China.

出版信息

Oncotarget. 2017 Jun 27;8(26):43295-43305. doi: 10.18632/oncotarget.17177.

Abstract

Tet methylcytosine dioxygenase2 gene (TET2) is one of the most frequently mutated gene in myeloid neoplasm, but the prognostic role of TET2 aberrations in myelodysplastic syndromes (MDS) remains unclear. Therefore, we performed a meta-analysis. Fourteen eligible studies with 1983 patients were included in this meta-analysis. Among these, 2 studies evaluated the impact that the TET2 expression level had on the prognosis. The combined hazard ratios (HR) estimated for overall survival (OS) was 1.00 (95%CI: 0.74 to 1.37; p=0.989) when comparing those with TET2 mutations with those without. Among the patients treated with hypomethylating agents (HMAs) or hematopoietic stem cell transplantation (HSCT), the pooled HR for OS was 1.02 (95% CI: 0.77-1.35, p=0.89) and 1.54 (95%CI: 0.69 to 3.44; p=0.29), respectively. We also conducted an analysis of the response rate to HMAs, and the OR was 1.73 (95%CI: 1.11 to 2.70; p=0.016). Additionally, subgroup analyses showed the pooled HR for OS was 0.93(95%CI: 0.44 to 1.98; P=0.849) in WHO-classified CMML patients and 1.02(95%CI: 1.02 to 3.46; p=0.042) in studies evaluated TET2 expression level. The analysis suggested TET2 mutations had no significant prognostic value on MDS. However, the response rates to HMAs were significantly different between those with and without TET2 mutations, and the low expression level of TET2 gene was significantly associated with a poor OS in MDS patients.

摘要

四甲基胞嘧啶双加氧酶2基因(TET2)是髓系肿瘤中最常发生突变的基因之一,但TET2异常在骨髓增生异常综合征(MDS)中的预后作用仍不清楚。因此,我们进行了一项荟萃分析。本荟萃分析纳入了14项符合条件的研究,共1983例患者。其中,2项研究评估了TET2表达水平对预后的影响。在比较有TET2突变者和无TET2突变者时,总生存(OS)的合并风险比(HR)估计为1.00(95%CI:0.74至1.37;p=0.989)。在接受去甲基化药物(HMA)或造血干细胞移植(HSCT)治疗的患者中,OS的汇总HR分别为1.02(95%CI:0.77-1.35,p=0.89)和1.54(95%CI:0.69至3.44;p=0.29)。我们还对HMA的缓解率进行了分析,比值比(OR)为1.73(95%CI:1.11至2.70;p=0.016)。此外,亚组分析显示,在世界卫生组织(WHO)分类的慢性粒-单核细胞白血病(CMML)患者中,OS的汇总HR为0.93(95%CI:0.44至1.98;P=0.849),在评估TET2表达水平的研究中为1.02(95%CI:1.02至3.46;p=0.042)。分析表明,TET2突变对MDS无显著预后价值。然而,有TET2突变者和无TET2突变者对HMA的缓解率存在显著差异,且TET2基因低表达水平与MDS患者的不良OS显著相关。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6ee6/5522146/fd02069302a9/oncotarget-08-43295-g001.jpg

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