Primary Objective

Mutations in the nucleophosmin 1 gene (NPM1) are common and recurrent molecular abnormalities in acute myeloid leukemia (AML). They are considered to be positive prognostic factors potentially due to immune responses mediated by NPM1_mut-specific cytotoxic T cells and thereby suppressing NPM1_mut-positive hematopoiesis.

In a large HLA association study, we compared the distribution of HLA class I alleles at 2-field-resolution between NPM1_mut-positive AML patients (n=471) and a control group of healthy individuals (n=51,890). HLA class I molecules of alleles which are underrepresented might present NPM1_mut-derived neoepitopes more effectively and have the potential to elicit an anti-leukemic immune response. We found HLA-B*40:01 and HLA-C*03:04 underrepresented in NPM1_mut-positive AML suggesting that neoepitopes presented by these HLA alleles trigger T cell responses. Our findings suggest that further studies are warranted to confirm the presence and functionality of neo-epitope specific T-cells.

The results were presented as a poster at the European Federation for Immunogenetics (EFI) in 2022 . A manuscript is in preparation, publication is planned for 2024.