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    Strong association of the HLA-DP6 supertype with childhood leukaemia is due to a single allele, DPB1*0601.

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    Authors
    Taylor, G M
    Hussain, A
    Verhage, V
    Thompson, P D
    Fergusson, W D
    Watkins, Gillian R
    Lightfoot, T
    Harrison, Christine J
    Birch, Jillian M
    Affiliation
    Cancer Immunogenetics Group, School of Cancer and Imaging Sciences, University of Manchester, St Mary's Hospital, Manchester, UK. gmtaylor@manchester.ac.uk
    Issue Date
    2009-05
    
    Metadata
    Show full item record
    Abstract
    We 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.
    Citation
    Strong association of the HLA-DP6 supertype with childhood leukaemia is due to a single allele, DPB1*0601. 2009, 23 (5):863-9 Leukemia
    Journal
    Leukemia
    URI
    http://hdl.handle.net/10541/87566
    DOI
    10.1038/leu.2008.374
    PubMed ID
    19148140
    Type
    Article
    Language
    en
    ISSN
    1476-5551
    ae974a485f413a2113503eed53cd6c53
    10.1038/leu.2008.374
    Scopus Count
    Collections
    All Paterson Institute for Cancer Research
    Academic Department of Radiation Oncology - ADRO

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