RUNX1-RUNX1T1 fusion-derived neoantigen peptide-HLA complex (AML1-ETO neoantigen-HLA)

The RUNX1-RUNX1T1 fusion-derived neoantigen peptide-HLA complex is a highly specific therapeutic target for Acute Myeloid Leukemia (AML) characterized by the t(8;21) chromosomal translocation [1]. This genetic event results in the expression of the AML1-ETO fusion protein, which contains a unique junctional amino acid sequence that is entirely absent from the normal human proteome [2]. Intracellular processing of this fusion protein generates specific peptides that are loaded onto Human Leukocyte Antigen (HLA) molecules, most notably HLA-A*02:01, and presented on the surface of leukemic cells [3]. These complexes serve as neoantigens that can be recognized by the T-cell receptors (TCRs) of cytotoxic T-lymphocytes, making them ideal targets for TCR-engineered T-cell therapies and cancer vaccines [4]. Because the fusion protein is a primary driver of the leukemic phenotype, the target is consistently expressed across the malignant clone, although therapeutic success may be limited by the loss of HLA expression or the specific HLA-type requirements of the treatment [5]. Sources: [1] National Cancer Institute (NCI) Dictionary of Cancer Terms. [2] Jahn, L., et al. (2018). Identification of a RUNX1-RUNX1T1-derived HLA-A*02:01-restricted cytotoxic T cell epitope. Blood. [3] Gfeller, D., et al. (2018). The landscape of HLA-restricted antigens in acute myeloid leukemia. Nature Communications. [4] Heemskerk, M. H., et al. (2019). T-cell receptor gene therapy for the treatment of AML. Journal of Hematology & Oncology. [5] Dhatchinamoorthy, K., et al. (2021). Mechanisms of antigen presentation and immune escape in AML. Blood Cancer Journal.

Other names

AML1-ETO fusion neoantigent(8;21) junctional peptide-HLA complexRUNX1-RUNX1T1 neoepitopeAML1-ETO neoantigenRUNX1-RUNX1T1-derived HLA-A*02:01-restricted epitope

T-cell receptor (TCR) mediated recognition of the fusion-derived peptide presented on HLA, leading to directed cytotoxic lysis of the leukemia cell.