dc.contributor.author | Wojdacz, TK | |
dc.contributor.author | Amarasinghe, HE | |
dc.contributor.author | Kadalayil, L | |
dc.contributor.author | Beattie, A | |
dc.contributor.author | Forster, J | |
dc.contributor.author | Blakemore, SJ | |
dc.contributor.author | Parker, H | |
dc.contributor.author | Bryant, D | |
dc.contributor.author | Larrayoz, M | |
dc.contributor.author | Clifford, R | |
dc.contributor.author | Robbe, P | |
dc.contributor.author | Davis, ZA | |
dc.contributor.author | Else, M | |
dc.contributor.author | Howard, DR | |
dc.contributor.author | Stamatopoulos, B | |
dc.contributor.author | Steele, AJ | |
dc.contributor.author | Rosenquist, R | |
dc.contributor.author | Collins, A | |
dc.contributor.author | Pettitt, AR | |
dc.contributor.author | Hillmen, P | |
dc.contributor.author | Plass, C | |
dc.contributor.author | Schuh, A | |
dc.contributor.author | Catovsky, D | |
dc.contributor.author | Oscier, DG | |
dc.contributor.author | Rose-Zerilli, MJJ | |
dc.contributor.author | Oakes, CC | |
dc.contributor.author | Strefford, JC | |
dc.date.accessioned | 2019-12-13T14:17:03Z | |
dc.date.issued | 2019-08-27 | |
dc.identifier.citation | Blood Advances, 2019, 3 (16), pp. 2474 - 2481 | |
dc.identifier.issn | 2473-9529 | |
dc.identifier.uri | https://repository.icr.ac.uk/handle/internal/3471 | |
dc.identifier.eissn | 2473-9537 | |
dc.identifier.doi | 10.1182/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.extent | 2474 - 2481 | |
dc.language | eng | |
dc.language.iso | eng | |
dc.publisher | American Society of Hematology | |
dc.rights.uri | https://creativecommons.org/licenses/by/4.0 | |
dc.title | Clinical significance of DNA methylation in chronic lymphocytic leukemia patients: results from 3 UK clinical trials | |
dc.type | Journal Article | |
rioxxterms.versionofrecord | 10.1182/bloodadvances.2019000237 | |
rioxxterms.licenseref.uri | https://creativecommons.org/licenses/by/4.0 | |
rioxxterms.licenseref.startdate | 2019-08-27 | |
rioxxterms.type | Journal Article/Review | |
dc.relation.isPartOf | Blood Advances | |
pubs.issue | 16 | |
pubs.notes | Not 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-status | Published | |
pubs.volume | 3 | |
pubs.embargo.terms | Not known | |
icr.researchteam | Biology of Childhood Leukaemia | |
dc.contributor.icrauthor | Else, Monica | |