Direct evidence that leukemic cells present HLA-associated immunogenic peptides derived from the BCR-ABL b3a2 fusion protein

The BCR-ABL oncogene is central in the pathogenesis of chronic myeloid leuk emia (CML). Here, tandem nanospray mass spectrometry was used to demonstrat e cell surface HLA-associated expression of the BCR-ABL peptide KQSSKALQR o n class I-negative CIVIL cells transfected with HLA-A*0301, and on primary CIVIL cells from HLA-A3-positive patients. These patients mounted a cytotox ic T-lymphocyte response to KQSSKALQR that also killed autologous CML cells , and tetramer staining demonstrated the presence of circulating KQSSKALQR- specific T cells. The findings are the first demonstration that CML cells e xpress HLA-associated leukemia-specific immunogenic peptides and provide a sound basis for immunization studies against BCR-ABL. (C) 2001 by The Ameri can Society of Hematology.