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

2.50
Hdl Handle:
http://hdl.handle.net/10541/87566
Title:
Strong association of the HLA-DP6 supertype with childhood leukaemia is due to a single allele, DPB1*0601.
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
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.
Affiliation:
Cancer Immunogenetics Group, School of Cancer and Imaging Sciences, University of Manchester, St Mary's Hospital, Manchester, UK. gmtaylor@manchester.ac.uk
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
Issue Date:
May-2009
URI:
http://hdl.handle.net/10541/87566
DOI:
10.1038/leu.2008.374
PubMed ID:
19148140
Type:
Article
Language:
en
ISSN:
1476-5551
Appears in Collections:
All Paterson Institute for Cancer Research; Academic Department of Radiation Oncology - ADRO

Full metadata record

DC FieldValue Language
dc.contributor.authorTaylor, G Men
dc.contributor.authorHussain, Aen
dc.contributor.authorVerhage, Ven
dc.contributor.authorThompson, P Den
dc.contributor.authorFergusson, W Den
dc.contributor.authorWatkins, Gillian Ren
dc.contributor.authorLightfoot, Ten
dc.contributor.authorHarrison, Christine Jen
dc.contributor.authorBirch, Jillian Men
dc.date.accessioned2009-12-08T12:24:19Z-
dc.date.available2009-12-08T12:24:19Z-
dc.date.issued2009-05-
dc.identifier.citationStrong association of the HLA-DP6 supertype with childhood leukaemia is due to a single allele, DPB1*0601. 2009, 23 (5):863-9 Leukemiaen
dc.identifier.issn1476-5551-
dc.identifier.pmid19148140-
dc.identifier.doi10.1038/leu.2008.374-
dc.identifier.urihttp://hdl.handle.net/10541/87566-
dc.description.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.en
dc.language.isoenen
dc.subjectAcute Myeloid Leukaemiaen
dc.subjectPrecursor Cell Lymphoblastic Leukaemia-Lymphomaen
dc.subject.meshAlleles-
dc.subject.meshAmino Acid Sequence-
dc.subject.meshCase-Control Studies-
dc.subject.meshChild-
dc.subject.meshDisease Susceptibility-
dc.subject.meshHLA-DP Antigens-
dc.subject.meshHaplotypes-
dc.subject.meshHumans-
dc.subject.meshInfant, Newborn-
dc.subject.meshLeukemia, Myeloid, Acute-
dc.subject.meshMolecular Sequence Data-
dc.subject.meshPrecursor Cell Lymphoblastic Leukemia-Lymphoma-
dc.subject.meshSequence Homology, Amino Acid-
dc.titleStrong association of the HLA-DP6 supertype with childhood leukaemia is due to a single allele, DPB1*0601.en
dc.typeArticleen
dc.contributor.departmentCancer Immunogenetics Group, School of Cancer and Imaging Sciences, University of Manchester, St Mary's Hospital, Manchester, UK. gmtaylor@manchester.ac.uken
dc.identifier.journalLeukemiaen

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