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Lookup NU author(s): Professor Julie Irving,
Dr Amir Enshaei,
Dr Amy Erhorn,
Professor Christine Harrison FRCPath FMedSci,
Professor Anthony Moorman
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Somatic genetic abnormalities are initiators and drivers of disease and have proven clinical utility atinitial diagnosis. However, the genetic landscape and its clinical utility at relapse is less wellunderstood and has not been studied comprehensively. We analysed cytogenetic data from 427children with relapsed B-cell precursor ALL treated on the international trial, ALLR3. Also wescreened 238 patients with a marrow relapse for selected copy number alterations (CNA) andmutations. Cytogenetic risk groups were predictive of outcome post-relapse and survival rates at 5years for patients with good, intermediate and high risk cytogenetics were 68%, 47% and 26%,p<0.001. TP53 alterations and NR3C1/BTG1 deletions were associated with a higher risk ofprogression: hazard ratio 2.36 (95% CI 1.51-3.70), p<0.001 and 2.15 (1.32-3.48), p=0.002. NRASmutations were associated with an increased risk of progression among standard risk patients withhigh hyperdiploidy: 3.17 (1.15-8.71), p=0.026. Patients classified clinically as standard and high riskhad distinct genetic profiles. The outcome of clinical standard risk patients with high riskcytogenetics was equivalent to clinical high risk patients. Screening patients at relapse for keygenetic abnormalities will enable the integration of genetic and clinical risk factors to improvepatient stratification and outcome.
Author(s): Irving JAE, Enshaei A, Parker CA, Sutton R, Kuiper RP, Erhorn A, Minto L, Venn NC, Law T, Yu J, Schwab C, Davies R, Matheson E, Davies A, Sonneveld E, den Boer ML, Love SB, Harrison CJ, Hoogerbrugge PM, Revesz T, Saha V, Moorman AV
Publication type: Article
Publication status: Published
Print publication date: 18/08/2016
Online publication date: 26/05/2016
Acceptance date: 19/05/2016
Date deposited: 16/06/2016
ISSN (print): 0006-4971
ISSN (electronic): 1528-0020
Publisher: American Society of Hematology
Notes: Irving and Enshaei contributed equally to this study.
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