CYTOTOXIC T-CELL RESPONSE AGAINST THE CHIMERIC P210 BCR-ABL PROTEIN IN PATIENTS WITH CHRONIC MYELOGENOUS LEUKEMIA

Human chronic myelogenous leukemia (CML) is characterized by a translo cation between chromosomes 9 and 22 that results in a BCR-ABL fusion g ene coding for chimeric proteins. The junctional region of the BCR-ABL (b3a2) molecule represents a potential leukemia-specific antigen which could be recognized by cytotoxic T lymphocytes (CTL), In fact, we ide ntified a junctional nonapeptide (SSKALQRPV) which binds to HLA-A2.1 m olecules, This peptide, as well as those binding to HLA-A3, -A11, and -B8 molecules (previously identified by others), elicits primary CTL r esponses in vitro from PBLs of both healthy donors and CML patients, S uch CTL recognize KLA-matched, BCR-ABL-positive leukemic cells, implyi ng efficient natural processing and presentation of these junctional p eptides. Specific CTL were found at high frequency in 5 of 21 CML pati ents, suggesting that these epitopes are, to some extent, immunogenic in vivo during the course of the disease. These peptides could be usef ul for the development of specific immunotherapy in CML patients.