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

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HLA-DR1-restricted bcr-abl (b3a2)-specific CD4+ T lymphocytes respond to dendritic cells pulsed with b3a2 peptide and antigen-presenting cells exposed to b3a2 containing cell lysates.

Chronic myeloid leukemia (CML) is characterized by a specific translocation of the c-abl oncogene on chromosome 9 to the break point cluster region (bcr) on chromosome 22, t(9;22) (q34;q11). This translocation results in the expression of a 210-kD bcr-abl protein fusion gene product. The juxtaposition of the bcr and abl genes produces a novel junctional amino acid sequence, which may be present...

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BCR/ABL-specific peptides KQSSKALQR to HLA-A*0301 and GFKQSSKAL to HLA-B*0801. Proteasomal digestion showed cleavage sites leading to KQSSKALQR but not to GFKQSSKAL. Using mass spectrometry KQSSKALQR

Chronic myeloid leukemia (CML) is a malignant disease caused by dysregulation of a pluripotent hematopoietic precursor cell. CML is characterized by the Philadelphia chromosome, containing the t(9;22) translocation, resulting in the chimeric BCR/ABL oncogene. This translocation has been found to be essential and sufficient for the development of CML. Depending on the exons of the BCR and ABL ge...

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HLA class II-restricted antigen presentation of endogenous bcr-abl fusion protein by chronic myelogenous leukemia-derived dendritic cells to CD4(+) T lymphocytes.

Bcr-abl fusion peptide-specific CD4+ T-lymphocyte clones have recently been shown to augment colony formation by chronic myelogenous leukemia (CML) cells in a bcr-abl type-specific and HLA class II-restricted manner without addition of exogenous antigen. These findings suggest that CML cells can naturally process and present endogenous bcr-abl fusion protein to CD4+ T lymphocytes in the context...

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Recognition of BCR-ABL positive leukemic blasts by human CD4+ T cells elicited by primary in vitro immunization with a BCR-ABL breakpoint peptide.

In chronic myeloid leukemia (CML) the classical 9;22 translocation results in a BCR-ABL fusion gene, which encodes chimeric BCR-ABL fusion 210 kD oncoproteins (p210BCR-ABL). The two main p210BCR-ABL fusion variants in CML, b2a2 and b3a2 are examples of well characterized antigens expressed by malignant cells. The possibility of an immunotherapeutic approach involving the fusion part of p210BCR-...

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Circulating bcr-abl-specific CD8+ T cells in chronic myeloid leukemia patients and healthy subjects.

BACKGROUND AND OBJECTIVES The fusion oncoprotein bcr-abl that characterizes chronic myeloid leukemia (CML) is a leukemia-specific antigen, which may be immunogenic in vivo. KQSSKALQR and GFKQSSKAL, peptide sequences spanning the b3a2 bcr-abl junction, have affinity for HLA-A3 and HLA-B8, respectively, and we have shown the presence of KQSSKALQR on the surface of CML cells. We analyzed the exist...

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ژورنال

عنوان ژورنال: Blood

سال: 2001

ISSN: 1528-0020,0006-4971

DOI: 10.1182/blood.v98.10.2887