HLA class I and II molecules presenting BCR-ABL p210 b3a2 breakpoint-derived peptides (HLA-BCR-ABL (b3a2))

The target consists of Human Leukocyte Antigen (HLA) Class I and II molecules presenting specific junctional peptides derived from the b3a2 breakpoint of the BCR-ABL p210 fusion protein (Bocchia et al., 1995). This fusion protein is the primary driver of Chronic Myeloid Leukemia (CML) and occurs in a subset of Acute Lymphoblastic Leukemia (ALL) cases (Pinilla-Ibarz et al., 2000). Because the b3a2 junctional sequence is unique to the malignant clone and not found in healthy cells, it functions as a tumor-specific neoantigen. HLA Class I molecules present these peptides to CD8+ cytotoxic T cells, while HLA Class II molecules present them to CD4+ helper T cells (Rojas et al., 2007). Therapeutic interventions, such as peptide vaccines, aim to stimulate the patient's immune system to recognize these complexes and destroy leukemic cells. Experimental adoptive cell therapies, including TCR-engineered T cells, are also being developed to target this specific peptide-HLA interface. While tyrosine kinase inhibitors are effective at controlling CML, targeting the BCR-ABL neoantigen provides a strategy for eradicating minimal residual disease. This approach is highly dependent on the patient's HLA genotype, as specific HLA alleles are required to successfully bind and present the b3a2 peptides. Clinical challenges include the relatively low immunogenicity of these peptides and the potential for leukemic cells to downregulate HLA expression to evade immune detection.

Other names

BCR-ABL b3a2 neoantigenp210 b3a2 junctional peptide-HLA complexBCR-ABL fusion peptide-MHC complexe14a2 junctional peptide

Induction of peptide-specific CD4+ and CD8+ T-cell responses to recognize and eliminate leukemic cells expressing the BCR-ABL fusion protein (Pinilla-Ibarz et al., 2000).