目的:探讨伴有TET2基因TET_JBP结构域完全缺失(ΔJBP)的急性髓系白血病(AML)患者的临床特征与预后价值。方法:应用高通量测序技术(NGS)检测与AML相关的34种基因(包括TET2基因)突变的情况,利用I-TASSER工具对TET2蛋白全长及TET_JBP结构...目的:探讨伴有TET2基因TET_JBP结构域完全缺失(ΔJBP)的急性髓系白血病(AML)患者的临床特征与预后价值。方法:应用高通量测序技术(NGS)检测与AML相关的34种基因(包括TET2基因)突变的情况,利用I-TASSER工具对TET2蛋白全长及TET_JBP结构缺失体进行蛋白质三级结构的预测。结果:38例伴TET2突变的AML患者中,发生截短突变者22例(57.9%),其中16例(72.7%)产生TET2ΔJBP截短突变体,蛋白质结构预测显示,TET_JBP结构域缺失导致TET2蛋白三级结构明显改变。与非ΔJBP组患者相比,ΔJBP组患者年龄更高(63 vs 54岁,P=0.047),CEBPA双突变(CEBPA^(dm))的发生频率更高(31.3%vs 0,P=0.009),诱导化疗后完全缓解(CR)率更低(37.5%vs 81.8%,P=0.008),中位无事件生存期(EFS)(5 vs 19个月,P=0.000)及中位总生存期(OS)更短(16 vs 22个月,P=0.041)。单因素分析表明,血小板<50×10^(9)/L(P=0.004)、伴有CEBPA^(dm) (P=0.001)与更短的OS相关,进一步COX多因素分析提示,CEBPA^(dm)是影响TET2ΔJBP患者OS的独立预后因素(P=0.003)。此外,伴有CEBPA^(dm)的ΔJBP患者较不伴CEBPA^(dm)者呈现更低的血红蛋白水平(62 vs 75 g/L,P=0.030)和更短的中位OS(9 vs 18个月,P=0.000)。结论:具有TET2ΔJBP截短突变体的AML患者诱导化疗后CR率较低、EFS和OS较短,可能与预后不良相关,易发生CEBPA^(dm)共突变,且后者是TET2ΔJBP突变AML患者OS的独立影响因素。展开更多
与年龄相关的不确定潜能的克隆性造血(clonal hematopoiesis of indeterminate potential,CHIP)能通过激活炎症促进动脉粥样硬化的发生、发展,从而增加心脑血管疾病风险。作为最常见的CHIP相关突变的表观遗传调控基因之一,甲基胞嘧啶双...与年龄相关的不确定潜能的克隆性造血(clonal hematopoiesis of indeterminate potential,CHIP)能通过激活炎症促进动脉粥样硬化的发生、发展,从而增加心脑血管疾病风险。作为最常见的CHIP相关突变的表观遗传调控基因之一,甲基胞嘧啶双加氧酶2(ten-eleven translocation-2,TET2)基因突变可通过组蛋白去乙酰化作用增加巨噬细胞中IL-1β等促炎因子的转录,加速动脉粥样硬化斑块的形成,并与卒中风险增加及预后不良有关。未来通过靶向TET2基因及其相关机制通路可能有助于发现降低卒中风险或改善卒中预后的新途径。展开更多
Objective To investigate the expression of TET2 mRNA and protein in the bone marrow mononuclear cells(BMMNC) of patients with myelodysplastic syndrome(MDS) and its clinical significance. Methods The expression of TET2...Objective To investigate the expression of TET2 mRNA and protein in the bone marrow mononuclear cells(BMMNC) of patients with myelodysplastic syndrome(MDS) and its clinical significance. Methods The expression of TET2 mRNA and protein in bone marrow mononuclear cells(BMMNC) of 32 patients with MDS and 20 healthy donors was examined by qPCR and Western blot. Results The expression of TET2 mRNA in BMMNC was down-regulated in MDS patients compared with the donor group [(0.41±0.28)%vs.(1.07±0.56)%](P<0.001).Compared with lower expression group(TET2<0.4)[(6.53±6.17)%],patients with higher expression of TET2(≥0.4) presented significantly lower proportion of bone marrow blasts[(1.21±1.56)%](P<0.05).The expression of TET2 mRNA in BMMNC of MDS patients was inversely correlated with malignant clone burden(r=-0.398,P<0.05) and IPSS(r=-0.412, P<0.05).The expression of TET2 protein was down-regulated in MDS patients compared with that in the donor group. Conclusions The mRNA and protein expression of TET2 in BMMNC of MDS patients is decreased,which might be useful as an important parameter for the evaluation of MDS clone burden.展开更多
文摘目的:探讨伴有TET2基因TET_JBP结构域完全缺失(ΔJBP)的急性髓系白血病(AML)患者的临床特征与预后价值。方法:应用高通量测序技术(NGS)检测与AML相关的34种基因(包括TET2基因)突变的情况,利用I-TASSER工具对TET2蛋白全长及TET_JBP结构缺失体进行蛋白质三级结构的预测。结果:38例伴TET2突变的AML患者中,发生截短突变者22例(57.9%),其中16例(72.7%)产生TET2ΔJBP截短突变体,蛋白质结构预测显示,TET_JBP结构域缺失导致TET2蛋白三级结构明显改变。与非ΔJBP组患者相比,ΔJBP组患者年龄更高(63 vs 54岁,P=0.047),CEBPA双突变(CEBPA^(dm))的发生频率更高(31.3%vs 0,P=0.009),诱导化疗后完全缓解(CR)率更低(37.5%vs 81.8%,P=0.008),中位无事件生存期(EFS)(5 vs 19个月,P=0.000)及中位总生存期(OS)更短(16 vs 22个月,P=0.041)。单因素分析表明,血小板<50×10^(9)/L(P=0.004)、伴有CEBPA^(dm) (P=0.001)与更短的OS相关,进一步COX多因素分析提示,CEBPA^(dm)是影响TET2ΔJBP患者OS的独立预后因素(P=0.003)。此外,伴有CEBPA^(dm)的ΔJBP患者较不伴CEBPA^(dm)者呈现更低的血红蛋白水平(62 vs 75 g/L,P=0.030)和更短的中位OS(9 vs 18个月,P=0.000)。结论:具有TET2ΔJBP截短突变体的AML患者诱导化疗后CR率较低、EFS和OS较短,可能与预后不良相关,易发生CEBPA^(dm)共突变,且后者是TET2ΔJBP突变AML患者OS的独立影响因素。
基金supported by grants from the National Natural Science Foundation of China(No.30971286, 30971285,81170472)Chinese Medical Association of Molecular Biology Clinical Application Research Special Funds(No.CAMB042010)+1 种基金The"Eleventh Five-year Plan"National Science and Technology Support Plan(No. 2008BA161B00)Health Industry Research Special Project (No.201002024)
文摘Objective To investigate the expression of TET2 mRNA and protein in the bone marrow mononuclear cells(BMMNC) of patients with myelodysplastic syndrome(MDS) and its clinical significance. Methods The expression of TET2 mRNA and protein in bone marrow mononuclear cells(BMMNC) of 32 patients with MDS and 20 healthy donors was examined by qPCR and Western blot. Results The expression of TET2 mRNA in BMMNC was down-regulated in MDS patients compared with the donor group [(0.41±0.28)%vs.(1.07±0.56)%](P<0.001).Compared with lower expression group(TET2<0.4)[(6.53±6.17)%],patients with higher expression of TET2(≥0.4) presented significantly lower proportion of bone marrow blasts[(1.21±1.56)%](P<0.05).The expression of TET2 mRNA in BMMNC of MDS patients was inversely correlated with malignant clone burden(r=-0.398,P<0.05) and IPSS(r=-0.412, P<0.05).The expression of TET2 protein was down-regulated in MDS patients compared with that in the donor group. Conclusions The mRNA and protein expression of TET2 in BMMNC of MDS patients is decreased,which might be useful as an important parameter for the evaluation of MDS clone burden.
