HLA-DPB1 supertype-associated protection from childhood leukaemia: relationship to leukaemia karyotype and implications for prevention.

2.50
Hdl Handle:
http://hdl.handle.net/10541/58673
Title:
HLA-DPB1 supertype-associated protection from childhood leukaemia: relationship to leukaemia karyotype and implications for prevention.
Authors:
Taylor, Malcolm B; Harrison, Christine J; Eden, Tim O B; Birch, Jillian M; Greaves, Mel F; Lightfoot, Tracy; Hussain, Adiba
Abstract:
Most childhood B cell precursor (BCP) acute lymphoblastic leukaemia (ALL) cases carry the reciprocal translocation t(12;21)(p13;q22) ( approximately 25%), or a high hyperdiploid (HeH) karyotype (30%). The t(12;21) translocation leads to the expression of a novel fusion gene, TEL-AML1 (ETV6-RUNX1), and HeH often involves tri- and tetrasomy for chromosome 21. The presence of TEL-AML1+ and HeH cells in utero prior to the development of leukaemia suggests that these lesions play a critical role in ALL initiation. Based on our previous analysis of HLA-DP in childhood ALL, and evidence from in vitro studies that TEL-AML1 can activate HLA-DP-restricted T cell responses, we hypothesised that the development of TEL-AML1+ ALL might be influenced by the child's DPB1 genotype. To test this, we analysed the frequency of six HLA-DPB1 supertypes in a population-based series of childhood leukaemias (n = 776) classified by their karyotype (TEL-AML1+, HeH and others), in comparison with newborn controls (n = 864). One DPB1 supertype (GKD) conferred significant protection against TEL-AML1+ ALL (odds ratio (OR), 95% confidence interval (95% CI): 0.42, 0.22-0.81; p < 0.005) and HeH ALL (OR; 95% CI: 0.44, 0.30-0.65; p < 0.0001). These negative associations were almost entirely due to a single allele, DPB1*0101. Our results suggest that DPB1*0101 may afford protection from the development of TEL-AML1+ and HeH BCP ALL, possibly as the result of a DP-restricted immune response to BCP ALL-associated antigen(s), the identification of which could have important implications for the design of prophylactic vaccines.
Affiliation:
Cancer Immunogenetics Laboratory, St Mary's Hospital, University of Manchester, Manchester, M13 0JH, UK. gmtaylor@manchester.ac.uk
Citation:
HLA-DPB1 supertype-associated protection from childhood leukaemia: relationship to leukaemia karyotype and implications for prevention. 2008, 57 (1):53-61 Cancer Immunol. Immunother.
Journal:
Cancer Immunology, Immunotherapy
Issue Date:
Jan-2008
URI:
http://hdl.handle.net/10541/58673
DOI:
10.1007/s00262-007-0349-5
PubMed ID:
17622527
Type:
Article
Language:
en
ISSN:
0340-7004
Appears in Collections:
All Christie Publications

Full metadata record

DC FieldValue Language
dc.contributor.authorTaylor, Malcolm B-
dc.contributor.authorHarrison, Christine J-
dc.contributor.authorEden, Tim O B-
dc.contributor.authorBirch, Jillian M-
dc.contributor.authorGreaves, Mel F-
dc.contributor.authorLightfoot, Tracy-
dc.contributor.authorHussain, Adiba-
dc.date.accessioned2009-04-01T22:50:52Z-
dc.date.available2009-04-01T22:50:52Z-
dc.date.issued2008-01-
dc.identifier.citationHLA-DPB1 supertype-associated protection from childhood leukaemia: relationship to leukaemia karyotype and implications for prevention. 2008, 57 (1):53-61 Cancer Immunol. Immunother.en
dc.identifier.issn0340-7004-
dc.identifier.pmid17622527-
dc.identifier.doi10.1007/s00262-007-0349-5-
dc.identifier.urihttp://hdl.handle.net/10541/58673-
dc.description.abstractMost childhood B cell precursor (BCP) acute lymphoblastic leukaemia (ALL) cases carry the reciprocal translocation t(12;21)(p13;q22) ( approximately 25%), or a high hyperdiploid (HeH) karyotype (30%). The t(12;21) translocation leads to the expression of a novel fusion gene, TEL-AML1 (ETV6-RUNX1), and HeH often involves tri- and tetrasomy for chromosome 21. The presence of TEL-AML1+ and HeH cells in utero prior to the development of leukaemia suggests that these lesions play a critical role in ALL initiation. Based on our previous analysis of HLA-DP in childhood ALL, and evidence from in vitro studies that TEL-AML1 can activate HLA-DP-restricted T cell responses, we hypothesised that the development of TEL-AML1+ ALL might be influenced by the child's DPB1 genotype. To test this, we analysed the frequency of six HLA-DPB1 supertypes in a population-based series of childhood leukaemias (n = 776) classified by their karyotype (TEL-AML1+, HeH and others), in comparison with newborn controls (n = 864). One DPB1 supertype (GKD) conferred significant protection against TEL-AML1+ ALL (odds ratio (OR), 95% confidence interval (95% CI): 0.42, 0.22-0.81; p < 0.005) and HeH ALL (OR; 95% CI: 0.44, 0.30-0.65; p < 0.0001). These negative associations were almost entirely due to a single allele, DPB1*0101. Our results suggest that DPB1*0101 may afford protection from the development of TEL-AML1+ and HeH BCP ALL, possibly as the result of a DP-restricted immune response to BCP ALL-associated antigen(s), the identification of which could have important implications for the design of prophylactic vaccines.en
dc.language.isoenen
dc.subjectHLA-DPB1en
dc.subjectChildhood Leukaemiaen
dc.subjectImmune Responseen
dc.subjectTEL-AML1en
dc.subject.meshChild-
dc.subject.meshChromosome Aberrations-
dc.subject.meshCore Binding Factor Alpha 2 Subunit-
dc.subject.meshFemale-
dc.subject.meshGenetic Predisposition to Disease-
dc.subject.meshHLA-DP Antigens-
dc.subject.meshHumans-
dc.subject.meshIn Situ Hybridization, Fluorescence-
dc.subject.meshInfant, Newborn-
dc.subject.meshKaryotyping-
dc.subject.meshMale-
dc.subject.meshOncogene Proteins, Fusion-
dc.subject.meshPrecursor Cell Lymphoblastic Leukemia-Lymphoma-
dc.subject.meshReverse Transcriptase Polymerase Chain Reaction-
dc.titleHLA-DPB1 supertype-associated protection from childhood leukaemia: relationship to leukaemia karyotype and implications for prevention.en
dc.typeArticleen
dc.contributor.departmentCancer Immunogenetics Laboratory, St Mary's Hospital, University of Manchester, Manchester, M13 0JH, UK. gmtaylor@manchester.ac.uken
dc.identifier.journalCancer Immunology, Immunotherapyen

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