Definition of a possible genetic basis for susceptibility to acute myelogenous leukemia associated with the presence of a polymorphic Ia epitope.
The polymorphic Ia epitope recognized by monoclonal antibody 109d6 is detectable on the leukemic cells of a significantly increased number of individuals with acute myelogenous leukemia, compared with its frequency in normal healthy control individuals. In control individuals, the presence of the 109d6 epitope is closely correlated with but not identical to the DRw53 allo-specificity. However, the frequency of particular conventional Ia allodeterminants, including DRw53, is not significantly elevated in the leukemia group. Considerable evidence supports the conclusion that the high frequency of the 109d6 epitope reflects an inherited basis for susceptibility to the development of acute myelogenous leukemia and not a differentiation event occurring in the leukemic lineage. The 109d6 determinant is expressed by leukemic myeloblasts as well as by homologous normal B cells and monocytes obtained from the same individuals during remission of the leukemia. Furthermore, in healthy family members the 109d6 epitope is encoded by Ia haplotypes that are shared with the patient. Of special interest, certain of these haplotypes have combinations of the 109d6 epitope and Ia specificities not commonly seen in normal individuals; here, also, healthy family members share these haplotypes.
S
S
Seremetis
J
J
Cuttner
R
R
Winchester
D000911:Antibodies, Monoclonal / Q000276:immunology; D000912:Antibodies, Neoplasm / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology; D002454:Cell Differentiation; D003601:Cytotoxicity Tests, Immunologic; D004198:Disease Susceptibility; D000939:Epitopes / Q000235:genetics / Q000276:immunology; D008040:Genetic Linkage; D006684:HLA-DR Antigens; D000949:Histocompatibility Antigens Class II / Q000235:genetics* / Q000276:immunology; D006801:Humans; D007938:Leukemia / Q000276:immunology; D015470:Leukemia, Myeloid, Acute / Q000235:genetics* / Q000276:immunology; D009000:Monocytes / Q000276:immunology
D000911:Antibodies, Monoclonal; D000912:Antibodies, Neoplasm; D000939:Epitopes; D006684:HLA-DR Antigens; D000949:Histocompatibility Antigens Class II