急性淋巴细胞白血病是儿童常见的血液系统恶性肿瘤。最常见的遗传改变基因之一是PAX5基因。PAX5基因的表达贯穿B细胞发育的整个过程,其改变包括拷贝数变异、重排、基因内扩增、选择性剪切和点突变等。PAX5与伴侣基因产生融合蛋白通过干...急性淋巴细胞白血病是儿童常见的血液系统恶性肿瘤。最常见的遗传改变基因之一是PAX5基因。PAX5基因的表达贯穿B细胞发育的整个过程,其改变包括拷贝数变异、重排、基因内扩增、选择性剪切和点突变等。PAX5与伴侣基因产生融合蛋白通过干扰白血病细胞中正常PAX5蛋白的转录活性而发挥竞争性抑制剂的作用。PAX5基因相关的B-ALL亚型PAX5 P80R在儿童病例中与较差预后相关,PAX5alt亚型患者被归为高风险的频率高于标准风险。本文就PAX5基因在急性淋巴细胞白血病中的发病机制、融合基因及治疗策略进行综述。Acute lymphoblastic leukemia (ALL) is a common hematologic malignancy in children, with one of the most frequently altered genes being the PAX5 gene. The expression of the PAX5 gene is involved throughout the entire process of B-cell development, and its alterations include copy number variations, rearrangements, intragenic amplifications, alternative splicing, and point mutations. The fusion proteins formed by PAX5 and its partner genes act as competitive inhibitors by interfering with the normal transcriptional activity of the PAX5 protein in leukemic cells. The PAX5 gene-related B-ALL subtype PAX5 P80R was associated with a poorer prognosis in childhood cases, and patients with the PAX5alt subtype were classified as high risk more often than the standard risk. This review summarizes the role of the PAX5 gene in the pathogenesis of ALL, its fusion genes, and related therapeutic strategies.展开更多
目的观察胃癌患者血浆配对盒蛋白5(paired box protein 5,PAX5)与环指蛋白180(ring finger protein 180,RNF180)基因甲基化情况,探讨其与临床病理特征及预后的关系。方法110例胃癌患者为胃癌组,同期体检健康者50例为对照组,采用甲基化...目的观察胃癌患者血浆配对盒蛋白5(paired box protein 5,PAX5)与环指蛋白180(ring finger protein 180,RNF180)基因甲基化情况,探讨其与临床病理特征及预后的关系。方法110例胃癌患者为胃癌组,同期体检健康者50例为对照组,采用甲基化特异性PCR法检测血浆PAX5与RNF180基因甲基化状态,分析其与胃癌患者临床病理特征的关系。随访3年,采用Kaplan-Meier生存曲线分析PAX5、RNF180甲基化与患者预后的关系。结果胃癌患者血浆PAX5、RNF180基因启动子区甲基化发生率(70.00%、62.73%)高于对照组(32.00%、30.00%)(P<0.05),胃癌组TNM分期Ⅰ~Ⅱ期患者血浆PAX5、RNF180基因甲基化发生率(65.17%、57.30%)低于TNM分期Ⅲ~Ⅳ期患者(90.48%、85.71%)(P<0.05),胃癌组男性与女性、年龄<55岁与≥55岁、肿瘤直径<2.5 cm与≥2.5 cm、细胞低-中分化与高分化及有无淋巴结转移患者血浆PAX5、RNF180基因甲基化发生率比较差异均无统计学意义(P>0.05)。发生PAX5基因甲基化的胃癌患者3年生存率(68.83%)低于未发生甲基化患者(84.85%)(P<0.05),发生RNF180基因甲基化的胃癌患者3年总体生存率(73.91%)与未发生甲基化胃癌患者(73.17%)比较差异无统计学意义(P>0.05)。结论胃癌患者血浆PAX5与RNF180基因甲基化发生率增高,与肿瘤TNM分期有关,发生PAX5基因甲基化的患者3年总生存率低。展开更多
文摘急性淋巴细胞白血病是儿童常见的血液系统恶性肿瘤。最常见的遗传改变基因之一是PAX5基因。PAX5基因的表达贯穿B细胞发育的整个过程,其改变包括拷贝数变异、重排、基因内扩增、选择性剪切和点突变等。PAX5与伴侣基因产生融合蛋白通过干扰白血病细胞中正常PAX5蛋白的转录活性而发挥竞争性抑制剂的作用。PAX5基因相关的B-ALL亚型PAX5 P80R在儿童病例中与较差预后相关,PAX5alt亚型患者被归为高风险的频率高于标准风险。本文就PAX5基因在急性淋巴细胞白血病中的发病机制、融合基因及治疗策略进行综述。Acute lymphoblastic leukemia (ALL) is a common hematologic malignancy in children, with one of the most frequently altered genes being the PAX5 gene. The expression of the PAX5 gene is involved throughout the entire process of B-cell development, and its alterations include copy number variations, rearrangements, intragenic amplifications, alternative splicing, and point mutations. The fusion proteins formed by PAX5 and its partner genes act as competitive inhibitors by interfering with the normal transcriptional activity of the PAX5 protein in leukemic cells. The PAX5 gene-related B-ALL subtype PAX5 P80R was associated with a poorer prognosis in childhood cases, and patients with the PAX5alt subtype were classified as high risk more often than the standard risk. This review summarizes the role of the PAX5 gene in the pathogenesis of ALL, its fusion genes, and related therapeutic strategies.
文摘目的观察胃癌患者血浆配对盒蛋白5(paired box protein 5,PAX5)与环指蛋白180(ring finger protein 180,RNF180)基因甲基化情况,探讨其与临床病理特征及预后的关系。方法110例胃癌患者为胃癌组,同期体检健康者50例为对照组,采用甲基化特异性PCR法检测血浆PAX5与RNF180基因甲基化状态,分析其与胃癌患者临床病理特征的关系。随访3年,采用Kaplan-Meier生存曲线分析PAX5、RNF180甲基化与患者预后的关系。结果胃癌患者血浆PAX5、RNF180基因启动子区甲基化发生率(70.00%、62.73%)高于对照组(32.00%、30.00%)(P<0.05),胃癌组TNM分期Ⅰ~Ⅱ期患者血浆PAX5、RNF180基因甲基化发生率(65.17%、57.30%)低于TNM分期Ⅲ~Ⅳ期患者(90.48%、85.71%)(P<0.05),胃癌组男性与女性、年龄<55岁与≥55岁、肿瘤直径<2.5 cm与≥2.5 cm、细胞低-中分化与高分化及有无淋巴结转移患者血浆PAX5、RNF180基因甲基化发生率比较差异均无统计学意义(P>0.05)。发生PAX5基因甲基化的胃癌患者3年生存率(68.83%)低于未发生甲基化患者(84.85%)(P<0.05),发生RNF180基因甲基化的胃癌患者3年总体生存率(73.91%)与未发生甲基化胃癌患者(73.17%)比较差异无统计学意义(P>0.05)。结论胃癌患者血浆PAX5与RNF180基因甲基化发生率增高,与肿瘤TNM分期有关,发生PAX5基因甲基化的患者3年总生存率低。
