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dc.contributor.authorWojdacz, TK
dc.contributor.authorAmarasinghe, HE
dc.contributor.authorKadalayil, L
dc.contributor.authorBeattie, A
dc.contributor.authorForster, J
dc.contributor.authorBlakemore, SJ
dc.contributor.authorParker, H
dc.contributor.authorBryant, D
dc.contributor.authorLarrayoz, M
dc.contributor.authorClifford, R
dc.contributor.authorRobbe, P
dc.contributor.authorDavis, ZA
dc.contributor.authorElse, M
dc.contributor.authorHoward, DR
dc.contributor.authorStamatopoulos, B
dc.contributor.authorSteele, AJ
dc.contributor.authorRosenquist, R
dc.contributor.authorCollins, A
dc.contributor.authorPettitt, AR
dc.contributor.authorHillmen, P
dc.contributor.authorPlass, C
dc.contributor.authorSchuh, A
dc.contributor.authorCatovsky, D
dc.contributor.authorOscier, DG
dc.contributor.authorRose-Zerilli, MJJ
dc.contributor.authorOakes, CC
dc.contributor.authorStrefford, JC
dc.date.accessioned2019-12-13T14:17:03Z
dc.date.issued2019-08-27
dc.identifier.citationBlood Advances, 2019, 3 (16), pp. 2474 - 2481
dc.identifier.issn2473-9529
dc.identifier.urihttps://repository.icr.ac.uk/handle/internal/3471
dc.identifier.eissn2473-9537
dc.identifier.doi10.1182/bloodadvances.2019000237
dc.description.abstract<jats:title>Abstract</jats:title> <jats:p>Chronic lymphocytic leukemia patients with mutated immunoglobulin heavy-chain genes (IGHV-M), particularly those lacking poor-risk genomic lesions, often respond well to chemoimmunotherapy (CIT). DNA methylation profiling can subdivide early-stage patients into naive B-cell–like CLL (n-CLL), memory B-cell–like CLL (m-CLL), and intermediate CLL (i-CLL), with differing times to first treatment and overall survival. However, whether DNA methylation can identify patients destined to respond favorably to CIT has not been ascertained. We classified treatment-naive patients (n = 605) from 3 UK chemo and CIT clinical trials into the 3 epigenetic subgroups, using pyrosequencing and microarray analysis, and performed expansive survival analysis. The n-CLL, i-CLL, and m-CLL signatures were found in 80% (n = 245/305), 17% (53/305), and 2% (7/305) of IGHV-unmutated (IGHV-U) cases, respectively, and in 9%, (19/216), 50% (108/216), and 41% (89/216) of IGHV-M cases, respectively. Multivariate Cox proportional analysis identified m-CLL as an independent prognostic factor for overall survival (hazard ratio [HR], 0.46; 95% confidence interval [CI], 0.24-0.87; P = .018) in CLL4, and for progression-free survival (HR, 0.25; 95% CI, 0.10-0.57; P = .002) in ARCTIC and ADMIRE patients. The analysis of epigenetic subgroups in patients entered into 3 first-line UK CLL trials identifies m-CLL as an independent marker of prolonged survival and may aid in the identification of patients destined to demonstrate prolonged survival after CIT.</jats:p>
dc.format.extent2474 - 2481
dc.languageeng
dc.language.isoeng
dc.publisherAmerican Society of Hematology
dc.rights.urihttps://creativecommons.org/licenses/by/4.0
dc.titleClinical significance of DNA methylation in chronic lymphocytic leukemia patients: results from 3 UK clinical trials
dc.typeJournal Article
rioxxterms.versionofrecord10.1182/bloodadvances.2019000237
rioxxterms.licenseref.urihttps://creativecommons.org/licenses/by/4.0
rioxxterms.licenseref.startdate2019-08-27
rioxxterms.typeJournal Article/Review
dc.relation.isPartOfBlood Advances
pubs.issue16
pubs.notesNot known
pubs.organisational-group/ICR
pubs.organisational-group/ICR/Primary Group
pubs.organisational-group/ICR/Primary Group/ICR Divisions
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Molecular Pathology
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Molecular Pathology/Biology of Childhood Leukaemia
pubs.organisational-group/ICR
pubs.organisational-group/ICR/Primary Group
pubs.organisational-group/ICR/Primary Group/ICR Divisions
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Molecular Pathology
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Molecular Pathology/Biology of Childhood Leukaemia
pubs.publication-statusPublished
pubs.volume3en_US
pubs.embargo.termsNot known
icr.researchteamBiology of Childhood Leukaemiaen_US
dc.contributor.icrauthorElse, Monicaen


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