BCR-ABL fusion protein peptide-MHC complex (BCR-ABL pMHC)

The BCR-ABL fusion protein peptide-MHC complex is a tumor-specific neoantigen resulting from the reciprocal translocation between chromosomes 9 and 22, known as the Philadelphia chromosome (t(9;22)). This genetic event creates a unique fusion junction in the BCR-ABL protein that is entirely absent in healthy cells, making it a highly specific target for immunotherapy (Bocchia et al., 2005). Peptides spanning this fusion junction are processed intracellularly and presented on the cell surface by Major Histocompatibility Complex (MHC) Class I and Class II molecules (Pinilla-Ibarz et al., 2000). Recognition of these pMHC complexes by the T-cell receptor (TCR) of CD8+ and CD4+ T cells can trigger a targeted cytotoxic immune response against leukemic cells. While small-molecule tyrosine kinase inhibitors (TKIs) like imatinib target the enzymatic activity of the BCR-ABL protein itself, therapies targeting the pMHC complex—including peptide vaccines and TCR-engineered T cells—aim to eradicate residual disease and leukemic stem cells that may persist despite TKI therapy (Quintarelli et al., 2000). This target is primarily relevant for patients with Chronic Myeloid Leukemia (CML) and Philadelphia chromosome-positive Acute Lymphoblastic Leukemia (Ph+ ALL). The clinical utility of this target is currently limited by HLA restriction, as specific peptides can only be presented by certain HLA alleles, but it remains a cornerstone of research into curative strategies for Philadelphia chromosome-positive malignancies.

Other names

BCR-ABL neoantigenPhiladelphia chromosome-derived neoantigenBCR-ABL junctional peptide-HLA complexp210 BCR-ABL peptide-MHCp190 BCR-ABL peptide-MHC

Induction of T-cell mediated cytotoxicity through the specific recognition of the BCR-ABL fusion junction peptide presented on MHC molecules (Bocchia et al., 2005).