Immunologic Characterization of the Tumor-Specific bcr-abl Junction in Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia

• Published in: Blood 1990-07, Vol.76 (1), p.136-141
• Main Authors: Van Denderen, Janneke, Van Der Plas, Dorien, Meeuwsen, Toon, Zegers, Netty, Boersma, Wim, Grosveld, Gerard, Van Ewijk, Willem
• Format: Article
• Language: English
• Subjects: Adult; Amino Acid Sequence; Amino Acids - analysis; Biological and medical sciences; Cell Line; Chimera - immunology; DNA - analysis; DNA - genetics; Gene Expression Regulation, Neoplastic; Hematologic and hematopoietic diseases; Humans; Immune Sera - immunology; Leukemia, Myelogenous, Chronic, BCR-ABL Positive - diagnosis; Leukemia, Myelogenous, Chronic, BCR-ABL Positive - genetics; Leukemia, Myelogenous, Chronic, BCR-ABL Positive - immunology; Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis; Male; Medical sciences; Middle Aged; Molecular Sequence Data; Peptides - analysis; Precipitin Tests; Precursor Cell Lymphoblastic Leukemia-Lymphoma - diagnosis; Precursor Cell Lymphoblastic Leukemia-Lymphoma - genetics; Precursor Cell Lymphoblastic Leukemia-Lymphoma - immunology; Protein-Tyrosine Kinases; Proto-Oncogene Proteins - genetics; Proto-Oncogene Proteins - immunology; Proto-Oncogene Proteins c-abl; Proto-Oncogene Proteins c-bcr; Recombinant Fusion Proteins - genetics; Recombinant Fusion Proteins - immunology
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood.V76.1.136.136

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.