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

The BCR-ABL fusion protein junctional peptide-MHC complex is a tumor-specific neoantigen target characteristic of Philadelphia chromosome-positive (Ph+) leukemias, including Chronic Myeloid Leukemia (CML) and Acute Lymphoblastic Leukemia (ALL) [PMID: 12855513]. This target is formed by the unique amino acid sequence at the junction of the BCR and ABL1 proteins, resulting from the t(9;22) chromosomal translocation [PMID: 10648393]. These junctional peptides are processed and presented on the cell surface by Major Histocompatibility Complex (MHC) Class I and Class II molecules, where they can be recognized by CD8+ and CD4+ T cells, respectively [PMID: 11133743]. Because the fusion sequence is not present in the normal human proteome, it provides an ideal target for immunotherapy with minimal risk of cross-reactivity with healthy tissues [PMID: 17488651]. Therapeutic approaches include peptide vaccines, such as CMLVax100, and investigational TCR-engineered T-cell therapies designed to enhance the host's immune surveillance against leukemic clones [PMID: 21670471]. While tyrosine kinase inhibitors (TKIs) are the primary treatment, targeting these pMHC complexes aims to eliminate minimal residual disease and potentially cure the disease by addressing TKI-resistant leukemic stem cells [PMID: 15572434].

Other names

BCR-ABL neoantigenPhiladelphia chromosome fusion peptideBCR-ABL junctional epitopeBCR-ABL1 fusion peptidep210 BCR-ABL junctional peptide

Induction of a specific T-cell mediated immune response against the unique fusion junction of the BCR-ABL protein presented on MHC molecules to eliminate leukemic cells.