Immunologic characterization of the tumor-specific bcr-abl junction in Philadelphia chromosome-positive acute lymphoblastic leukemia.
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.
Department of Immunology, Erasmus University, Rotterdam, The Netherlands.
J
J
van Denderen
D
D
van der Plas
T
T
Meeuwsen
N
N
Zegers
W
W
Boersma
G
G
Grosveld
W
W
van Ewijk
D000328:Adult; D000595:Amino Acid Sequence; D000596:Amino Acids / Q000032:analysis; D002460:Cell Line; D002678:Chimera / Q000276:immunology; D004247:DNA / Q000032:analysis / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007106:Immune Sera / Q000276:immunology; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000175:diagnosis / Q000235:genetics* / Q000276:immunology; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D010455:Peptides / Q000032:analysis; D011233:Precipitin Tests; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000175:diagnosis / Q000235:genetics* / Q000276:immunology; D011505:Protein-Tyrosine Kinases; D011518:Proto-Oncogene Proteins / Q000235:genetics* / Q000276:immunology; D016315:Proto-Oncogene Proteins c-abl; D051562:Proto-Oncogene Proteins c-bcr; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000276:immunology
D000596:Amino Acids; D007106:Immune Sera; D010455:Peptides; D011518:Proto-Oncogene Proteins; D011993:Recombinant Fusion Proteins; D004247:DNA; D011505:Protein-Tyrosine Kinases; D016315:Proto-Oncogene Proteins c-abl; C496613:BCR protein, human; D051562:Proto-Oncogene Proteins c-bcr