NATURE OF HLA-ASSOCIATED PREDISPOSITION TO CHILDHOOD ACUTE LYMPHOBLASTIC-LEUKEMIA

A molecular analysis was carried out in 63 sequentially diagnosed chil dhood acute lymphoblastic leukemia (ALL) patients and 1011 controls to investigate the homozygosity rate for HLA-DR53. HLA-DR53 is associate d with acute myeloblastic leukemia at the protein level, and our previ ous study has shown its association with early-onset chronic myeloid l eukemia 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. I n the common ALL group (n = 40), all seven DR53 homozygous patients we re 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 h omozygous for DR53. Heterozygous frequencies for HLA-DR53 were not dif ferent between patients and controls. Homozygosity for DR53 was associ ated 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 acid showed the recessive nature and the male predominance of the interact ive 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 dis-equilibrium with HLA-DR53 may be responsible for this association.