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Blood, 15 November 2001, Vol. 98, No. 10, pp. 2887-2893

PLENARY PAPER

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

Richard E. Clark, I. Anthony Dodi, Seran C. Hill, Jennie R. Lill, Geraldine Aubert, Andrew R. Macintyre, Jose Rojas, Audrey Bourdon, Philip L. R. Bonner, Lihui Wang, Stephen E. Christmas, Paul J. Travers, Colin S. Creaser, Robert C. Rees, and J. Alejandro Madrigal

From the Departments of Life Sciences and Chemistry and Physics, Nottingham Trent University, Nottingham, United Kingdom; Departments of Haematology and Immunology, University of Liverpool, Liverpool, United Kingdom; and The Anthony Nolan Research Institute, The Royal Free and University College Medical School, London, United Kingdom.

The BCR-ABL oncogene is central in the pathogenesis of chronic myeloid leukemia (CML). Here, tandem nanospray mass spectrometry was used to demonstrate cell surface HLA-associated expression of the BCR-ABL peptide KQSSKALQR on class I-negative CML cells transfected with HLA-A*0301, and on primary CML cells from HLA-A3-positive patients. These patients mounted a cytotoxic 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 express HLA-associated leukemia-specific immunogenic peptides and provide a sound basis for immunization studies against BCR-ABL.

© 2001 by The American Society of Hematology.
 

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