HLA Class I-presented BCR-ABL b3a2 fusion-junction peptide (BCR-ABL b3a2 neoantigen)

The HLA Class I-presented BCR-ABL b3a2 fusion-junction peptide is a tumor-specific neoantigen resulting from the t(9;22) chromosomal translocation, which creates the BCR-ABL1 fusion protein (National Cancer Institute, 2023). This specific breakpoint, also known as e14a2, joins exon 14 of the BCR gene to exon 2 of the ABL1 gene, producing a unique amino acid sequence at the junction that is absent in healthy tissues (Greco et al., 2021). These junctional peptides are processed by the proteasome and presented on the cell surface by Human Leukocyte Antigen (HLA) Class I molecules, such as HLA-A*02:01, where they can be recognized by CD8+ cytotoxic T lymphocytes (Rojas et al., 2007). Because the fusion sequence is truly neo-epitopic, it serves as a highly specific target for immunotherapies like peptide vaccines and T-cell receptor (TCR) engineered T cells (Bocchia et al., 2005). Targeting this complex is particularly relevant for eradicating leukemic stem cells in chronic myeloid leukemia (CML) and Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL) that persist despite tyrosine kinase inhibitor therapy (Quintarelli et al., 2012). However, therapeutic efficacy can be challenged by low antigen density and the potential for immune escape through HLA downregulation (Schetelig et al., 2008).

Other names

BCR-ABL b3a2 junctional peptidee14a2 BCR-ABL fusion peptidep210 BCR-ABL b3a2 neoantigenBCR-ABL fusion-junction neoepitope

Recognition of the specific peptide-HLA complex by T-cell receptors (TCRs) or TCR-like molecules to trigger targeted cytotoxic T-lymphocyte (CTL) mediated lysis of Philadelphia chromosome-positive malignant cells.