HLA-B8 and HLA-A3 Coexpressed With HLA-B8 Are Associated With a Reduced Risk of the Development of Chronic Myeloid Leukemia

摘要: Chronic myeloid leukemia (CML) is characterized by the chromosomal translocation t(9;22) resulting in chimeric bcr-abl oncogene that encodes P210 fusion protein, which contains a unique amino acid sequence. If peptides derived from leukemia-specific part of are expressed HLA molecules on cell membrane leukemic cells, an immunological response may occur. Recent studies using synthetic identical to region showed some capable binding HLA-A3, -A11, and -B8 molecules. Cytotoxic T-cell responses have been induced against bcr-abl-derived bound HLA-A3 -B8. We hypothesized if antigen processing protein leads presentation major histocompatibility complex (MHC) vivo, this be reflected diminished incidence CML individuals expressing or Consequently, lower frequencies these antigens would expected patients with compared unaffected individuals. A case-control study meta-analysis were performed test hypothesis. The multicenter data base European Group for Blood Marrow Transplantation (EBMT) registry Bone Donors Worldwide. Patients controls matched per country. consisted five reported literature. consisting 1,899 512, 363 bone marrow donors as yielded odds ratios (ORs) 0.90 (95% confidence interval [CI], 0.80 1.00) 1.16 CI, 1.02 1.33) HLA-A11, OR 0.73 0.65 0. 82) HLA-B8. Coexpression HLA-B8 gave 0.51 0.40 0.67). This can translated protective effect 27% HLA-B8, 10% 49% protection combination comprising 463 4,912 29% risk reduction (OR 0.71; 95% 0.52 0.97), but 1.19 1.56) 1. 09 1.50) HLA-A11. In conclusion, results indicate expression, particular when coexpressed, associated CML. biological mechanism breakpoint induce immune response.