• Login
    View Item 
    •   Home
    • The Christie Research Publications Repository
    • All Christie Publications
    • View Item
    •   Home
    • The Christie Research Publications Repository
    • All Christie Publications
    • View Item
    JavaScript is disabled for your browser. Some features of this site may not work without it.

    Browse

    All of ChristieCommunitiesTitleAuthorsIssue DateSubmit DateSubjectsThis CollectionTitleAuthorsIssue DateSubmit DateSubjectsProfilesView

    My Account

    LoginRegister

    Local Links

    The Christie WebsiteChristie Library and Knowledge Service

    Statistics

    Display statistics

    HLA-DPβ1 Asp84-Lys69 antigen-binding signature predicts event-free survival in childhood B-cell precursor acute lymphoblastic leukaemia: results from the MRC UKALL XI childhood ALL trial.

    • CSV
    • RefMan
    • EndNote
    • BibTex
    • RefWorks
    Authors
    Taylor, G
    Wade, R
    Hussain, A
    Thompson, P
    Hann, I
    Gibson, B
    Eden, Tim O B
    Richards, S
    Issue Date
    2012-07
    
    Metadata
    Show full item record
    Abstract
    We previously reported that children in the UKALL XI ALL trial with HLA-DP 1 and -DP 3 supertypes had significantly worse event-free survival (EFS) than children with other DP supertypes. As DP 1 and DP 3 share two of four key antigen-binding amino-acid polymorphisms (aspartic acid84-lysine69), we asked whether Asp84-Lys69 or Asp84 alone were independent prognostic indicators in childhood acute lymphoblastic leukemia (ALL). We analysed EFS in 798 UKALL XI patients, stratified by Asp84-Lys69 vs non-Asp84-Lys69, for a median follow-up of 12.5 years. Asp84-Lys69 was associated with a significantly worse EFS than non-Asp84-Lys69 (5-year EFS: Asp84-Lys69: 58.8% (95% CI (confidence of interval): 52.7-64.9%); non-Asp84-Lys69: 67.3% (63.4-71.2%); 2P=0.007). Post-relapse EFS was 10% less in Asp84-Lys69 than non-Asp84-Lys69 patients. EFS was significantly worse (P=0.03) and post-relapse EFS marginally worse (P=0.06) in patients with Asp84 compared with Gly84. These results suggest that Asp84-Lys69 predicted adverse EFS in the context of UKALL XI because of Asp84, and may have influenced post-relapse EFS. We speculate that this may be due to the recruitment of Asp84-Lys69-restricted regulatory T cells in the context of this regimen, leading to the re-emergence of residual disease. However, functional and molecular studies of the prognostic value of this and other HLA molecular signatures in other childhood ALL trials are needed.
    Citation
    HLA-DPβ1 Asp84-Lys69 antigen-binding signature predicts event-free survival in childhood B-cell precursor acute lymphoblastic leukaemia: results from the MRC UKALL XI childhood ALL trial. 2012, 2 (7): Blood Cancer J
    Journal
    Blood Cancer Journal
    URI
    http://hdl.handle.net/10541/259277
    DOI
    10.1038/bcj.2012.25
    PubMed ID
    22852049
    Type
    Article
    Language
    en
    ISSN
    2044-5385
    ae974a485f413a2113503eed53cd6c53
    10.1038/bcj.2012.25
    Scopus Count
    Collections
    All Christie Publications

    entitlement

    Related articles

    • 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
    • Successful treatment without cranial radiotherapy of children receiving intensified chemotherapy for acute lymphoblastic leukaemia: results of the risk-stratified randomized central nervous system treatment trial MRC UKALL XI (ISRC TN 16757172).
    • Authors: Hill FG, Richards S, Gibson B, Hann I, Lilleyman J, Kinsey S, Mitchell C, Harrison CJ, Eden OB, UK Medical Research Council Working Party on Childhood Leukaemia
    • Issue date: 2004 Jan
    • Benefit of intensified treatment for all children with acute lymphoblastic leukaemia: results from MRC UKALL XI and MRC ALL97 randomised trials. UK Medical Research Council's Working Party on Childhood Leukaemia.
    • Authors: Hann I, Vora A, Richards S, Hill F, Gibson B, Lilleyman J, Kinsey S, Mitchell C, Eden OB
    • Issue date: 2000 Mar
    • Failure of a new protocol to improve treatment results in paediatric lymphoblastic leukaemia: lessons from the UK Medical Research Council trials UKALL X and UKALL XI.
    • Authors: Chessells JM, Harrison G, Richards SM, Gibson BE, Bailey CC, Hill FG, Hann IM, Medical Research Council Working Party On Childhood Leukaemia
    • Issue date: 2002 Aug
    • Comparison of allogeneic transplant versus chemotherapy for relapsed childhood acute lymphoblastic leukaemia in the MRC UKALL R1 trial. MRC Childhood Leukaemia Working Party.
    • Authors: Harrison G, Richards S, Lawson S, Darbyshire P, Pinkerton R, Stevens R, Oakhill A, Eden OB
    • Issue date: 2000 Aug
    DSpace software (copyright © 2002 - 2025)  DuraSpace
    Quick Guide | Contact Us
    Open Repository is a service operated by 
    Atmire NV
     

    Export search results

    The export option will allow you to export the current search results of the entered query to a file. Different formats are available for download. To export the items, click on the button corresponding with the preferred download format.

    By default, clicking on the export buttons will result in a download of the allowed maximum amount of items.

    To select a subset of the search results, click "Selective Export" button and make a selection of the items you want to export. The amount of items that can be exported at once is similarly restricted as the full export.

    After making a selection, click one of the export format buttons. The amount of items that will be exported is indicated in the bubble next to export format.