title: Nature of HLA-associated predisposition to childhood acute lymphoblastic leukemia.
abstract: A molecular analysis was carried out in 63 sequentially diagnosed childhood acute lymphoblastic leukemia (ALL) patients and 1011 controls to investigate the homozygosity rate for HLA-DR53. HLA-DR53 is associated with acute myeloblastic leukemia at the protein level, and our previous study has shown its association with early-onset chronic myeloid leukemia only in homozygous form at the DNA level. In the present study, the homozygosity rates for DR53 were 17.5 and 13.6% in patients and controls, respectively. Ten of the 11 homozygous patients were boys. In the common ALL group (n = 40), all seven DR53 homozygous patients were boys, and among 19 girls this genotype was not observed (P = 0.006). For males, homozygosity for DR53 revealed a relative risk (RR) of 3.29 (P = 0.008) for common ALL. Five of the 11 relapsed patients were homozygous for DR53. Heterozygous frequencies for HLA-DR53 were not different between patients and controls. Homozygosity for DR53 was associated with a very high relapse rate (45.5 vs 7.7%, P = 0.002, RR = 9.1). These results extended our findings in chronic myeloid leukemia and showed the recessive nature and the male predominance of the interactive HLA influence on the development of childhood leukemia. Molecular mimicry of an HLA-DR53 epitope by oncogenic (retro)viruses or putative susceptibility genes in linkage disequilibrium with HLA-DR53 may be responsible for this association.
authors.affiliation: Department of Haematology, University of Wales College of Medicine, Cardiff, UK.
authors.forename: M T
authors.initials: MT
authors.lastname: Dorak
authors.forename: G
authors.initials: G
authors.lastname: Owen
authors.forename: I
authors.initials: I
authors.lastname: Galbraith
authors.forename: N
authors.initials: N
authors.lastname: Henderson
authors.forename: D
authors.initials: D
authors.lastname: Webb
authors.forename: K I
authors.initials: KI
authors.lastname: Mills
authors.forename: C
authors.initials: C
authors.lastname: Darke
authors.forename: A K
authors.initials: AK
authors.lastname: Burnett
mesh_terms: D000293:Adolescent; D000328:Adult; D000483:Alleles; D004273:DNA, Neoplasm / Q000235:genetics; D005260:Female; D005808:Genes, Recessive; D005838:Genotype; D006683:HLA-DQ Antigens / Q000235:genetics; D059848:HLA-DQ alpha-Chains; D006684:HLA-DR Antigens / Q000235:genetics*; D059845:HLA-DRB4 Chains; D006720:Homozygote; D006801:Humans; D008297:Male; D008875:Middle Aged; D012150:Polymorphism, Restriction Fragment Length; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics*; D012016:Reference Values; D012307:Risk Factors; D012737:Sex Factors
chemical_list: D004273:DNA, Neoplasm; D006683:HLA-DQ Antigens; D059848:HLA-DQ alpha-Chains; C069050:HLA-DQA1 antigen; D006684:HLA-DR Antigens; C050610:HLA-DR53; D059845:HLA-DRB4 Chains