Genetic susceptibility to childhood common acute lymphoblastic leukaemia is associated with polymorphic peptide-binding pocket profiles in HLA-DPB1*0201.

2.50
Hdl Handle:
http://hdl.handle.net/10541/80232
Title:
Genetic susceptibility to childhood common acute lymphoblastic leukaemia is associated with polymorphic peptide-binding pocket profiles in HLA-DPB1*0201.
Authors:
Taylor, G Malcolm; Dearden, Simon; Ravetto, Paul F; Ayres, Michelle; Watson, Pamela; Hussain, Adiba; Greaves, Mel F; Alexander, F E; Eden, Tim O B
Abstract:
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 DPbeta1*0201 allotypic protein, suggesting that susceptibility to childhood c-ALL may be influenced by DPbeta ABS amino acid polymorphisms shared by DPbeta1*0201 and other DPbeta1 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 DPbeta1*0201-related allotypic proteins, leading to the activation of helper T cells mediating proliferative stress on preleukaemic cells.
Affiliation:
Immunogenetics Laboratory, St Mary's Hospital, Manchester M13 0JH, UK. gmtaylor@man.ac.uk
Citation:
Genetic susceptibility to childhood common acute lymphoblastic leukaemia is associated with polymorphic peptide-binding pocket profiles in HLA-DPB1*0201. 2002, 11 (14):1585-97 Hum. Mol. Genet.
Journal:
Human Molecular Genetics
Issue Date:
1-Jul-2002
URI:
http://hdl.handle.net/10541/80232
PubMed ID:
12075003
Type:
Article
Language:
en
ISSN:
0964-6906
Appears in Collections:
All Christie Publications

Full metadata record

DC FieldValue Language
dc.contributor.authorTaylor, G Malcolm-
dc.contributor.authorDearden, Simon-
dc.contributor.authorRavetto, Paul F-
dc.contributor.authorAyres, Michelle-
dc.contributor.authorWatson, Pamela-
dc.contributor.authorHussain, Adiba-
dc.contributor.authorGreaves, Mel F-
dc.contributor.authorAlexander, F E-
dc.contributor.authorEden, Tim O B-
dc.date.accessioned2009-09-08T10:05:50Z-
dc.date.available2009-09-08T10:05:50Z-
dc.date.issued2002-07-01-
dc.identifier.citationGenetic susceptibility to childhood common acute lymphoblastic leukaemia is associated with polymorphic peptide-binding pocket profiles in HLA-DPB1*0201. 2002, 11 (14):1585-97 Hum. Mol. Genet.en
dc.identifier.issn0964-6906-
dc.identifier.pmid12075003-
dc.identifier.urihttp://hdl.handle.net/10541/80232-
dc.description.abstractIn 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 DPbeta1*0201 allotypic protein, suggesting that susceptibility to childhood c-ALL may be influenced by DPbeta ABS amino acid polymorphisms shared by DPbeta1*0201 and other DPbeta1 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 DPbeta1*0201-related allotypic proteins, leading to the activation of helper T cells mediating proliferative stress on preleukaemic cells.en
dc.language.isoenen
dc.subjectAdult T-Cell Leukaemia Lymphomaen
dc.subjectPrecursor Cell Lymphoblastic Leukaemia-Lymphomaen
dc.subject.meshBinding Sites-
dc.subject.meshCase-Control Studies-
dc.subject.meshChild-
dc.subject.meshChild, Preschool-
dc.subject.meshCore Binding Factor Alpha 2 Subunit-
dc.subject.meshDiploidy-
dc.subject.meshFemale-
dc.subject.meshGene Rearrangement-
dc.subject.meshGenetic Predisposition to Disease-
dc.subject.meshHLA-DR Antigens-
dc.subject.meshHeterozygote-
dc.subject.meshHumans-
dc.subject.meshInfant-
dc.subject.meshLeukemia-Lymphoma, Adult T-Cell-
dc.subject.meshMale-
dc.subject.meshModels, Genetic-
dc.subject.meshOncogene Proteins, Fusion-
dc.subject.meshPeptides-
dc.subject.meshPolymorphism, Genetic-
dc.subject.meshPrecursor Cell Lymphoblastic Leukemia-Lymphoma-
dc.subject.meshReference Values-
dc.titleGenetic susceptibility to childhood common acute lymphoblastic leukaemia is associated with polymorphic peptide-binding pocket profiles in HLA-DPB1*0201.en
dc.typeArticleen
dc.contributor.departmentImmunogenetics Laboratory, St Mary's Hospital, Manchester M13 0JH, UK. gmtaylor@man.ac.uken
dc.identifier.journalHuman Molecular Geneticsen

Related articles on PubMed

All Items in Christie are protected by copyright, with all rights reserved, unless otherwise indicated.