van Denderen J, van der Plas D, Meeuwsen T, Zegers N, Boersma W, Grosveld G, van Ewijk W
Department of Immunology, Erasmus University, Rotterdam, The Netherlands.
Blood. 1990 Jul 1;76(1):136-41.
Philadelphia (Ph')-positive acute lymphoblastic leukemia (ALL) is highly associated with two forms of chimeric bcr-abl proteins: P190bcr-abl and P210bcr-abl. Whereas P210bcr-abl also occurs in chronic myeloid leukemia, P190bcr-abl is uniquely expressed in Ph'-positive ALL. As a consequence, P190bcr-abl is preeminently a tumor-specific marker in leukemic cells of ALL patients. Because P190bcr-abl is composed of the normal bcr and abl proteins, the major part of the P190bcr-abl molecule comprises nontumor-specific determinants. The joining region between bcr and abl, newly generated during the Ph' translocation, is exclusively a tumor-specific epitope on the P190bcr-abl molecule. Therefore, only antibodies against the bcr-abl joining region will detect the tumor-specificity of P190bcr-abl. In this study a polyclonal antiserum, termed BP-ALL, was raised against a synthetic peptide corresponding to the bcr-abl junction in P190bcr-abl. The reactivity of BP-ALL with native P190bcr-abl derived from a Ph'-positive ALL cell line (TOM-1) was tested using immunoprecipitation analysis. BP-ALL reacted highly specifically with P190bcr-abl but not with P210bcr-abl isolated from chronic myeloid leukemia cell lines. Peptide inhibition studies further confirmed the fine specificity of BP-ALL. Our data indicate that the tumor-specific bcr-abl junction domain is exposed in an antigenic fashion on the P190bcr-abl molecule.
费城（Ph'）阳性急性淋巴细胞白血病（ALL）与两种嵌合型bcr-abl蛋白密切相关：P190bcr-abl和P210bcr-abl。虽然P210bcr-abl也出现在慢性髓性白血病中，但P190bcr-abl仅在Ph'阳性ALL中表达。因此，P190bcr-abl是ALL患者白血病细胞中卓越的肿瘤特异性标志物。由于P190bcr-abl由正常的bcr和abl蛋白组成，P190bcr-abl分子的主要部分包含非肿瘤特异性决定簇。在Ph'易位过程中新产生的bcr与abl之间的连接区域是P190bcr-abl分子上唯一的肿瘤特异性表位。因此，只有针对bcr-abl连接区域的抗体才能检测P190bcr-abl的肿瘤特异性。在本研究中，制备了一种针对与P190bcr-abl中bcr-abl连接相对应的合成肽的多克隆抗血清，称为BP-ALL。使用免疫沉淀分析测试了BP-ALL与源自Ph'阳性ALL细胞系（TOM-1）的天然P190bcr-abl的反应性。BP-ALL与P190bcr-abl高度特异性反应，但不与从慢性髓性白血病细胞系分离的P210bcr-abl反应。肽抑制研究进一步证实了BP-ALL的精细特异性。我们的数据表明，肿瘤特异性的bcr-abl连接结构域以抗原形式暴露在P190bcr-abl分子上。
