Abstract
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.
Publication types
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Comparative Study
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Research Support, Non-U.S. Gov't
MeSH terms
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Adult
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Amino Acid Sequence
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Antigen Presentation*
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Antigens, Neoplasm / chemistry
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Antigens, Neoplasm / immunology*
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Antigens, Surface / chemistry
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Antigens, Surface / immunology*
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Female
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Fusion Proteins, bcr-abl / chemistry
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Fusion Proteins, bcr-abl / immunology*
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HLA-A3 Antigen / genetics
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HLA-A3 Antigen / immunology*
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Humans
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K562 Cells / immunology
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Leukemia, Myelogenous, Chronic, BCR-ABL Positive / genetics
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Leukemia, Myelogenous, Chronic, BCR-ABL Positive / immunology*
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Male
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Middle Aged
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Neoplasm Proteins / chemistry
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Neoplasm Proteins / immunology*
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Neoplastic Stem Cells / immunology*
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Peptide Fragments / chemistry
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Peptide Fragments / immunology*
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Recombinant Fusion Proteins / immunology
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Spectrometry, Mass, Electrospray Ionization
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T-Lymphocytes, Cytotoxic / immunology
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Transfection
Substances
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Antigens, Neoplasm
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Antigens, Surface
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HLA-A3 Antigen
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Neoplasm Proteins
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Peptide Fragments
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Recombinant Fusion Proteins
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Fusion Proteins, bcr-abl