Immunologic characterization of the tumor-specific bcr-abl junction in
Philadelphia chromosome-positive acute lymphoblastic leukemia
J van Denderen, D van der Plas, T Meeuwsen, N Zegers, W Boersma, G Grosveld and W van Ewijk
Department of Immunology, Erasmus University, Rotterdam, The Netherlands.
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.
Volume 76,
Issue 1,
pp. 136-141,
07/01/1990
Copyright © 1990 by The American Society of Hematology
