van Denderen J, ten Hacken P, Berendes P, Zegers N, Boersma W, Grosveld G, van Ewijk W
Department of Immunology, Erasmus University, Rotterdam, The Netherlands.
Leukemia. 1992 Nov;6(11):1107-12.
The reciprocal translocation between chromosome 9 and chromosome 22, as observed in chronic myeloid leukemia (CML) as well as in acute lymphoblastic leukemia (ALL), results in a 22q- chromosome, the so-called Philadelphia chromosome. The translocation event creates on the Philadelphia chromosome a fusion between two genes: bcr and abl. Depending on the localization of the breakpoint in the bcr gene different chimeric bcr-abl genes are generated, each encoding their own tumor-specific protein: e1-a2P190bcr-abl, b2-a2p210bcr-abl, or b3-a2P210bcr-abl. Especially in ALL, the presence of such a tumor-specific protein is highly associated with a poor prognosis. Detection of these proteins therefore has a strong clinical significance. In this study a polyclonal antiserum, termed BP-2, was raised against a synthetic peptide, corresponding to the tumor-specific 'fusion-point' epitope of the b3-a2P210bcr-abl protein. The specificity of BP-2 for the bcr-abl joining region in b3-a2P210bcr-abl is demonstrated by means of peptide inhibition studies in combination with immunoprecipitation. In addition we show the reactivity of BP-2 with bcr-abl proteins in leukemic cells of a Philadelphia-chromosome-positive ALL patient.
在慢性粒细胞白血病（CML）以及急性淋巴细胞白血病（ALL）中观察到的9号染色体与22号染色体之间的相互易位，会导致一条22号染色体长臂缺失的染色体，即所谓的费城染色体。这种易位事件在费城染色体上造成了两个基因bcr和abl的融合。根据bcr基因中断点的位置，会产生不同的嵌合bcr-abl基因，每个基因都编码其自身的肿瘤特异性蛋白：e1-a2P190bcr-abl、b2-a2p210bcr-abl或b3-a2P210bcr-abl。特别是在ALL中，这种肿瘤特异性蛋白的存在与预后不良高度相关。因此，检测这些蛋白具有很强的临床意义。在本研究中，制备了一种针对合成肽的多克隆抗血清，该合成肽对应于b3-a2P210bcr-abl蛋白的肿瘤特异性“融合点”表位。通过肽抑制研究结合免疫沉淀，证明了BP-2对b3-a2P210bcr-abl中bcr-abl连接区域的特异性。此外，我们展示了BP-2与一名费城染色体阳性ALL患者白血病细胞中的bcr-abl蛋白的反应性。
