Evidence for HLA-linked susceptibility factors in childhood leukemia.
To test the hypothesis that susceptibility to leukemia can be governed by (a) recessive gene(s) associated with the major histocompatibility complex (MHC) in man, we performed an analysis of the inheritance of HLA antigens in 55 families in which one of the children developed ALL. We found among the parents of affected children a highly significant increased compatibility at the DR locus (p = 0.003). A similar increase was observed in sharing HLA antigens of the B locus (p = 0.02). The observed number of homozygotes among the patients was twice the expected value in families where the parents shared a B and a DR antigen. In segregation analysis, heterozygotes for the shared parental HLA antigen were significantly more prevalent among the healthy siblings. Our genetical analysis indicates that mating of certain shared alleles of the HLA system (especially of the DR locus) is associated with the risk for the offspring to develop ALL in childhood. This situation favors the expression of recessive genes associated with the MHC, and presumably those involved in the susceptibility to acute leukemia. Because familial leukemia is a rare event, the susceptibility to childhood ALL must also implicate genes outside the MHC and important environmental factors.
D002648:Child; D005260:Female; D005802:Genes, MHC Class II; D005808:Genes, Recessive; D008040:Genetic Linkage; D006680:HLA Antigens / Q000235:genetics*; D015235:HLA-B Antigens; D006684:HLA-DR Antigens; D006801:Humans; D007945:Leukemia, Lymphoid / Q000235:genetics / Q000276:immunology*; D008297:Male; D011336:Probability
D006680:HLA Antigens; D015235:HLA-B Antigens; D006684:HLA-DR Antigens