Mutant nucleophosmin 1 peptide–HLA complex (NPM1mut peptide–HLA complex)

The mutant nucleophosmin 1 peptide–HLA complex is formed when a neoantigenic peptide sequence derived from a mutated form of nucleophosmin 1 (typically found in acute myeloid leukemia) is presented by a human leukocyte antigen (HLA) class I molecule on the surface of leukemic cells. NPM1 is a multifunctional nuclear chaperone protein whose most common cancer-associated mutations lead to the generation of novel C-terminal amino acid sequences, resulting in both protein mislocalization to the cytoplasm (NPMc+) and creation of leukemia-unique peptide neoepitopes. These mutant-specific peptides, such as CLAVEEVSL and AIQDLCLAV, can be presented via common HLA class I molecules (e.g., HLA-A*02:01), enabling T-cell–mediated immune targeting of malignant cells. The mutant NPM1 peptide–HLA complex thereby serves as a leukemia-specific antigen and a promising target for immunotherapeutic approaches in NPM1-mutated AML, though its applicability is strongly dependent on the particular HLA type of the patient. There are no approved drugs that directly target this complex, but experimental peptide vaccines and HLA-restricted T-cell therapies are under early investigation. The presence of mutant NPM1 peptide–HLA complexes classifies this as a targetable disease mechanism, especially in personalized immunotherapy contexts.

Other names

Mutant NPM1 peptide–HLA class I complexNPM1-mutated peptide–HLA complexNPM1mut–HLA complex

Presentation of leukemia-specific mutant peptide to cytotoxic T cells via HLA class I, activating anti-leukemic immune response.