TET2、ASXL1 和 EZH2 基因突变与中国人骨髓增生异常综合征。

TET2, ASXL1 and EZH2 mutations in Chinese with myelodysplastic syndromes.

机构信息

MDS and MPN Centre, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, China.

出版信息

Leuk Res. 2013 Mar;37(3):305-11. doi: 10.1016/j.leukres.2012.10.004. Epub 2012 Oct 23.

DOI:10.1016/j.leukres.2012.10.004

PMID:23099237

Abstract

Somatic mutations of epigenetic gene regulators are common in patients with myelodysplastic syndromes (MDS) and correlate with some clinical and laboratory features. We studied mutations in TET2, ASXL1 and EZH2 in 153 Chinese patients with MDS. TET2 mutations were detected in 35 patients (23%), ASXL1 in 33 patients (22%) and EZH2 in 8 (5%). ASXL1 mutations were associated with increased colony formation of BFU-E, CFU-E and CFU-GM (P-values, 0.049, 0.011 and 0.006). EZH2 mutations were common in patients with poor IPSS cytogenetics (P=0.001) and in patients in the IPSS intermediate-2/high-risk cohorts (P=0.06). In uni- but not multi-variate analyses, mutated TET2 was associated with longer survival (P=0.044) whereas EZH2 mutations were associated with an increased risk of transformation to acute myeloid leukemia (AML; P=0.039). These data suggest ASXL1 mutations might results in dominance of the mutant clone in Chinese with MDS whereas EZH2 mutations might predict an increased risk of transformation to AML.

摘要

体细胞突变的表观遗传学基因调控因子在骨髓增生异常综合征（MDS）患者中很常见，与一些临床和实验室特征相关。我们研究了 153 例中国 MDS 患者的 TET2、ASXL1 和 EZH2 突变。在 35 例患者（23%）中检测到 TET2 突变，在 33 例患者（22%）中检测到 ASXL1 突变，在 8 例患者（5%）中检测到 EZH2 突变。ASXL1 突变与 BFU-E、CFU-E 和 CFU-GM 的集落形成增加相关（P 值分别为 0.049、0.011 和 0.006）。EZH2 突变常见于 IPSS 细胞遗传学不良的患者（P=0.001）和 IPSS 中-2/高危组的患者（P=0.06）。在单变量但不是多变量分析中，突变的 TET2 与更长的生存时间相关（P=0.044），而 EZH2 突变与向急性髓系白血病（AML）转化的风险增加相关（P=0.039）。这些数据表明，ASXL1 突变可能导致中国 MDS 患者的突变克隆优势，而 EZH2 突变可能预示着向 AML 转化的风险增加。