Berendes P, Hoogeveen A, van Dijk M, van Denderen J, van Ewijk W
Department of Immunology, Erasmus University, Rotterdam, The Netherlands.
Leukemia. 1995 Aug;9(8):1321-7.
The t(1;19) translocation is the most commonly observed chromosomal translocation in childhood acute lymphoblastic leukemia (ALL). Its presence among pre-B cell ALL cases, has been associated with a poor prognosis. Two genes, E2A and PBX1, are involved in this t(1;19) translocation. As a consequence, parts of the E2A and PBX1 genes are fused, resulting in a chimeric E2A-PBX1 gene, encoding chimeric E2A-PBX1 proteins. As such, the amino acid sequence at the fusion site represents a unique tumor-specific determinant. We report on the generation of a polyclonal antiserum, termed BP 1/19, raised against the tumor-specific E2A-PBX1 junction of E2A-PBX1 proteins. The specificity of antiserum BP 1/19 for the E2A-PBX1 fusion-point is demonstrated at the peptide and at the protein level. Furthermore, specific binding of antiserum BP 1/19 to t(1;19) positive cells was shown using immunofluorescence techniques. The study shows that: (1) the tumor-specific fusion-point epitope on E2A-PBX1 proteins is presented in an antigenic fashion, and (2) this particular fusion-point epitope can be used in immunological marker analysis using fluorescence microscopy.
t(1;19)易位是儿童急性淋巴细胞白血病(ALL)中最常见的染色体易位。它在早前B细胞ALL病例中的存在与预后不良相关。两个基因,E2A和PBX1,参与了这种t(1;19)易位。因此,E2A和PBX1基因的部分片段融合,产生一个嵌合E2A-PBX1基因,编码嵌合E2A-PBX1蛋白。这样,融合位点的氨基酸序列代表了一个独特的肿瘤特异性决定簇。我们报告了一种多克隆抗血清的产生,称为BP 1/19,它是针对E2A-PBX1蛋白的肿瘤特异性E2A-PBX1连接点产生的。抗血清BP 1/19对E2A-PBX1融合点的特异性在肽和蛋白水平上得到了证实。此外,使用免疫荧光技术显示抗血清BP 1/19与t(1;19)阳性细胞有特异性结合。该研究表明:(1)E2A-PBX1蛋白上的肿瘤特异性融合点表位以抗原形式呈现,(2)这个特定的融合点表位可用于荧光显微镜下的免疫标记分析。