Proteinase 3 (Myeloblastin) (PR3)

Proteinase 3 (PR3), also known as Myeloblastin, is a 29 kDa serine protease primarily stored within the azurophilic granules of neutrophils and monocytes (UniProt: P24158). It plays a critical role in the innate immune response by degrading extracellular matrix components and processing pro-inflammatory cytokines such as TNF-alpha (PubMed: 10973284). In hematologic malignancies, PR3 is significantly overexpressed in the malignant blasts of patients with Acute Myeloid Leukemia (AML) and Chronic Myeloid Leukemia (CML), making it a valuable leukemia-associated antigen (PubMed: 10447203). Myeloblastin-derived peptides, most notably the HLA-A2-restricted nonamer PR1 (VLQELNVTV), are presented on the surface of these leukemic cells and serve as targets for various immunotherapeutic strategies. These strategies include PR1 peptide vaccines designed to elicit a cytotoxic T-lymphocyte response and TCR-like monoclonal antibodies, such as h8F4, that bind directly to the PR1/HLA-A2 complex (PubMed: 26712908). While targeting these peptides shows promise for treating myeloid leukemias, potential safety concerns include transient neutropenia due to PR3 expression in normal myeloid progenitors and the theoretical risk of inducing autoimmune responses similar to those seen in Granulomatosis with polyangiitis (PubMed: 17105821).

Other names

MyeloblastinPRTN3Neutrophil proteinase 3Wegener autoantigenPR1 peptideP29

Induction of peptide-specific cytotoxic T-lymphocyte (CTL) responses and direct targeting of peptide-MHC class I complexes on the surface of malignant myeloid cells.