Human Molecular Genetics, 2002, Vol. 11, No. 14 1585-1597
© 2002 Oxford University Press
Genetic susceptibility to childhood common acute lymphoblastic leukaemia is associated with polymorphic peptide-binding pocket profiles in HLA-DPB1*0201
1Immunogenetics Laboratory, St Mary's Hospital, Manchester M13 0JH, UK, 2Leukaemia Research Fund Centre at the Institute of Cancer Research, London, UK, 3Public Health Sciences, University of Edinburgh, Edinburgh, UK and 4Academic Department of Paediatric Oncology, Christie Hospital and Royal Manchester Children's Hospitals, Manchester, UK
Received November 4, 2001; Accepted April 22, 2002
In a previous study, we obtained preliminary evidence in a small series of patients (n=63) suggesting that susceptibility to childhood common acute lymphoblastic leukaemia (c-ALL) was associated with an allele at the HLA-DPB1 locus, DPB1*0201. We have now tested this hypothesis by comparing the frequency of children with leukaemia (n=982) who typed for specific DPB1 alleles and two groups of non-leukaemic children, one consisting of children with solid tumours, excluding lymphomas (n=409), the other consisting of normal infants (n=864). We found that significantly more children with c-ALL and T-ALL, but not pro-B ALL or acute non-ALL typed for DPB1*0201 as compared with children with solid tumours [odds ratio (OR), 95% confidence interval (CI) for c-ALL: 1.76, 1.20–2.56; T-ALL: 1.93, 1.01–3.80] and normal infants (OR, 95% CI for c-ALL: 1.83, 1.34–2.48; T-ALL: 2.00, 1.10–3.82). In childhood c-ALL, significantly more children than those with solid tumours or normal infants typed for DPB1 alleles coding specific polymorphic amino acids lining the antigen-binding site of the DPß1*0201 allotypic protein, suggesting that susceptibility to childhood c-ALL may be influenced by DPß ABS amino acid polymorphisms shared by DPß1*0201 and other DPß1 allotypes. These results point to a mechanism of c-ALL susceptibility that involves the presentation of specific antigenic peptides, possibly derived from infectious agents, by DPß1*0201-related allotypic proteins, leading to the activation of helper T cells mediating proliferative stress on preleukaemic cells.
* To whom correspondence should be addressed. Tel: +44 161 2766472; Fax: +44 161 2766414; Email: gmtaylor{at}man.ac.uk
For a full list of Investigators, see the end of the paper.
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