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
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.
