Z. Berke et al., Peptides spanning the junctional region of both the abl/bcr and the bcr/abl fusion proteins bind common HLA class I molecules, LEUKEMIA, 14(3), 2000, pp. 419-426
The Philadelphia (Ph) chromosome, resulting from the t(9;22) translocation,
is characteristic of chronic myeloid leukemia (CML), As a result of this t
ranslocation, two novel chimeric genes are generated and the bcr/abl and ab
l/bcr fusion proteins expressed. The bcr/abl fusion mRNA is present in all
CML patients, whereas the reciprocal abl/bcr fusion mRNA is detectable in a
bout 80% of the Ph+ CML patients. These fusion proteins may undergo enzymat
ic degradation in the cytosol and give rise to MHC class I restricted pepti
de epitopes originating from the junctional regions of the translocation pr
oducts, which thus may serve as novel tumor specific antigens. Previously,
other groups have tested peptides corresponding to the junctional region of
the bcr/abl protein for their binding capacity to HLA class I molecules an
d have identified a few candidate epitopes, Peptides originating from the a
bl/bcr fusion protein have on the other hand so far been neglected, for no
apparent reason. We have now extended these studies to include also the rec
iprocal abl/bcr translocation product by testing a large panel of synthetic
peptides corresponding to the junctional regions of both the abl/bcr and t
he bcr/abl fusion proteins for their ability to stabilize HLA class I molec
ules. We find that the abl/bcr translocation product may be an even more im
portant source of CML specific peptide antigens and together the junctional
sequences of both these proteins contain peptide sequences which bind effi
ciently to a number of HLA molecules (HLA-A1, -A2, -A3, -A11, -B7, -B27, -B
35) and thus may serve as candidate CML specific tumor antigens.