Strong association of the HLA-DP6 supertype with childhood leukaemia is due to a single allele, DPB1*0601.
AuthorsTaylor, G M
Thompson, P D
Fergusson, W D
Watkins, Gillian R
Harrison, Christine J
Birch, Jillian M
AffiliationCancer Immunogenetics Group, School of Cancer and Imaging Sciences, University of Manchester, St Mary's Hospital, Manchester, UK. email@example.com
MetadataShow full item record
AbstractWe previously reported that susceptibility to childhood B cell precursor ALL (BCP ALL) is associated with HLA-DPB1 alleles having glutamic acid (E) rather than lysine (K) in the P4 antigenic peptide-binding pocket. Clustering approximately 90% of DPB1 alleles into DPB69E (DP2, 6, 8) and DPB69K (DP1, 3, 4) supertypes revealed that DP2 and DP8 are associated with BCP ALL, but DP6 is also associated with non-BCP leukaemia. Here, we report that only one of seven alleles with the DP6 supertype (DPB1(*)0601) is associated with childhood leukaemia (leukaemia vs controls: odds ratio, 95% confidence interval [OR, CI]: 4.6, 2.0-10.4; corrected P=0.019), but not with childhood solid tumours or lymphomas. DPB1(*)0601 is also significantly associated with leukaemia subtypes, including BCP ALL, Pro-B ALL, T-ALL and AML. DPB1(*)0601 is significantly over-transmitted (76.9%) from parents to children with BCP ALL (OR; CI: 4.7; 1.01-22.2). Sequencing the coding region of DPB1(*)0601 revealed an exon 1-4 haplotype [T-DEAV-KIL-RVI] shared with DPB1(*)0301 and 0901, but no evidence of germline mutations in childhood leukaemia. These results suggest that the DPbeta0601 molecule may be functionally involved in childhood leukaemia. Analysis of peptide binding and T-cell activation by DPbeta0601-peptide complexes should help determine its role in childhood leukaemia causation.
CitationStrong association of the HLA-DP6 supertype with childhood leukaemia is due to a single allele, DPB1*0601. 2009, 23 (5):863-9 Leukemia
- HLA-DPB1 supertype-associated protection from childhood leukaemia: relationship to leukaemia karyotype and implications for prevention.
- Authors: Taylor M, Harrison C, Eden T, Birch J, Greaves M, Lightfoot T, Hussain A, UKCCS Investigators.
- Issue date: 2008 Jan
- Genetic susceptibility to childhood common acute lymphoblastic leukaemia is associated with polymorphic peptide-binding pocket profiles in HLA-DPB1*0201.
- Authors: Taylor GM, Dearden S, Ravetto P, Ayres M, Watson P, Hussain A, Greaves M, Alexander F, Eden OB, UKCCS Investigators. United Kingdom Childhood Cancer Study.
- Issue date: 2002 Jul 1
- Relationship between HLA-DP supertype and survival in childhood acute lymphoblastic leukaemia: evidence for selective loss of immunological control of residual disease?
- Authors: Taylor GM, Richards S, Wade R, Hussain A, Simpson J, Hill F, Mitchell C, Eden T, UKCCS and CCLG Investigators.
- Issue date: 2009 Apr
- HLA-associated susceptibility to childhood B-cell precursor ALL: definition and role of HLA-DPB1 supertypes.
- Authors: Taylor GM, Hussain A, Lightfoot TJ, Birch JM, Eden TO, Greaves MF
- Issue date: 2008 Mar 25
- Preliminary evidence of an association between HLA-DPB1*0201 and childhood common acute lymphoblastic leukaemia supports an infectious aetiology.
- Authors: Taylor GM, Robinson MD, Binchy A, Birch JM, Stevens RF, Jones PM, Carr T, Dearden S, Gokhale DA
- Issue date: 1995 Mar