E2A-PBX1融合基因阳性儿童急性淋巴细胞白血病携带变异型融合转.docVIP

E2A-PBX1融合基因阳性儿童急性淋巴细胞白血病携带变异型融合转 　 作者：李志刚，赵玮，吴敏媛，胡亚美 【摘要】 为了研究儿童急性淋巴细胞白血病（ALL）中E2A-PBX1融合基因的表达，采用位于E2A基因不同位置的上游引物与下游PBX1引物，检测了410例儿童ALL，包括362例B细胞ALL和48例T细胞ALL。结果发现： 17例患儿携带E2A-PBX1融合基因，检出率4.1%，且全部为B细胞ALL，而且所有阳性病例均表达一种变异型融合转录本，后者是由E2A基因的第13外显子（159 bp）被差异剪切形成的。经BLASTn比对分析，这种转录本保持了原来的开放阅读框，但导致53个氨基酸残基的丢失。这53个氨基酸残基位于活化区2，会导致融合蛋白中部分环-螺旋结构以及全部七聚体亮氨酸重复序列的丢失。结论：携带E2A-PBX1融合基因的儿童ALL表达典型和变异型2种融合转录本，后者是由E2A基因第13外显子被差异剪切而形成的，它将导致融合蛋白中53个氨基酸残基及其所构成的部分环-螺旋结构以及全部七聚体亮氨酸重复序列的丢失。 【关键词】 急性淋巴细胞白血病 　　Variant Fusion Transcript in ALL Children with E2A-PBX1 Fusion Gene Positive 　　Abstract The study was aimed to investigate the expression of E2A-PBX1 fusion gene in children with acute lymphoblastic leukemia (ALL). The primers located at different sites of E2A and PBX1 gene were used to screen for the fusion gene in 410 children with ALL，including 362 cases of B cell ALL and 48 cases of T cell ALL. The results showed that 17 children carried the fusion gene. The positive rate was 4.1%. Furthermore，all the positive cases expressed a variant type of fusion transcript. It resulted from different splicing of the 13th exon (159 bp) of E2A gene. Analyses with BLASTn indicated that the variant type of transcript retained the open reading frame. However，the loss of 53 amino acid residues which were located at the 2nd activation domain resulted in the partial deletion of the putative loop-helix (LH) structure as well as the complete deletion of the heptad leucine repeat. It is concluded that all the children with ALL positive for the E2A-PBX1 fusion gene express typical and variant fusion transcripts. The latter resulted from different splicing of the 13th exon (159 bp) of E2A gene. The loss of 53aa would lead to the partial deletion of the putative loop-helix (LH) structure as well as the complete deletion of the heptad leucine repeat. 　　Key words ALL; E2A-PBX1 fusion gene; variant type of fusion transcript; 2nd activation domain t(1;19)(q23;p13.3) 易位及其形成的E2A-PBX1融合基因是急性淋巴细胞白血病（ALL）中常见的染色体畸变及基因异