ANTIBODY RECOGNITION OF THE TUMORSPECIFIC bcr-abl JOINING REGION IN CHRONIC MYELOID LEUKEMIA By JANNEKE VAN DENDEREN,* ANDRÉ HERMANS,* TOON MEEUWSEN,* CHRISTINE TROELSTRA,* NETTY ZEGERS,1 WIM BOERSMA,1

Chronic myeloid leukemia (CML)' is a pluripotent stem cell disorder characterized by the presence of the Philadelphia (Ph') chromosome in the leukemic cells of 96% of all CML patients (1) . The Ph' chromosome is formed by a reciprocal translocation between chromosomes 22 and 9 (2, 3) . In this translocation, the c-abloncogene has moved from chromosome 9 into the breakpoint cluster region (bcr), within the bcr gene on chromosome 22, resulting in a chimeric bcr-c-abl gene (3, 4) . The fused gene encodes an 8.5-kb chimeric mRNA (5, 6), which is translated into a 210-kD protein (7) . This P210bcr-abl protein shows tyrosine kinase activity and is uniquely present in the leukemic cells of CML (and a number of Ph" ALL) patients (8-12) . The breakpoint in the bcr gene occurs either between bcr exon 2 (b2) and 3 (b3), or alternatively between bcr exon 3 (b3) and 4 (b4) . Therefore, in the mature bcr-abl mRNA, either b2 or b3 is spliced to abl exon a2, which results in two alternative chimeric P21Obrrabl proteins, comprising either the b2-a2 or b3-a2 junction (13). As such, the two different amino acid sequences at the point of the junction represent unique tumor-specific determinants . In this study we investigate whether these joining determinants are exposed on the P210b`r-abl molecule in an immunogenic fashion . Our data indicate that the joining determinants b2-a2 can indeed be recognized by antibodies . The strategy we used to generate and characterize the anti-b2-a2 antiserum has potential for the further development of antibodies detecting tumor-specific proteins resulting from chromosomal rearrangements .