RUNX1-RUNX1T1 fusion-derived neoantigen (RUNX1-RUNX1T1 neoantigen)

The RUNX1-RUNX1T1 fusion-derived neoantigen is a tumor-specific peptide resulting from the t(8;21)(q22;q22) chromosomal translocation, which is one of the most common genetic abnormalities in acute myeloid leukemia (AML) (Gao et al., 2023, Nature Communications). This translocation fuses the Runt-related transcription factor 1 (RUNX1) gene with the RUNX1 partner transcriptional co-repressor 1 (RUNX1T1) gene, creating a chimeric protein that disrupts normal hematopoiesis (NCI, 2024). Peptides spanning the fusion junction are processed by the cellular proteasome and presented on the cell surface by Human Leukocyte Antigen (HLA) molecules, such as HLA-A*02:01 (Pettersson et al., 2022, Blood). Because these junctional sequences are entirely absent in healthy cells, they serve as ideal neoantigens for targeted immunotherapy, significantly reducing the risk of off-target effects on normal tissues. Therapeutic strategies currently under investigation include TCR-engineered T-cells (TCR-T) and peptide vaccines designed to elicit a robust cytotoxic T-lymphocyte response against AML blasts. Targeting these neoantigens offers a precision medicine approach to treat t(8;21) AML, particularly in patients with minimal residual disease or those who have relapsed after conventional chemotherapy. The efficacy of these therapies depends on the stable expression of the fusion protein and the presence of specific HLA alleles to present the neoantigen to the immune system. Research has demonstrated that T-cells equipped with specific TCRs can selectively recognize and kill AML cells harboring the RUNX1-RUNX1T1 fusion while sparing normal hematopoietic stem cells (Gao et al., 2023).

Other names

AML1-ETO fusion neoantigent(8;21) fusion-derived peptideRUNX1-RUNX1T1 junctional neoantigenRUNX1-RUNX1T1 peptide-HLA complex

T-cell receptor (TCR) mediated recognition of the peptide-HLA complex leading to cytotoxic T-lymphocyte activation and lysis of leukemia cells.