Clinical significance of DNA methylation in chronic lymphocytic leukemia patients: Results from 3 UK clinical trials
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...
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ftunivbruxelles:oai:dipot.ulb.ac.be:2013/296789 2023-05-15T15:11:31+02:00 Clinical significance of DNA methylation in chronic lymphocytic leukemia patients: Results from 3 UK clinical trials Wojdacz, Tomasz Kazimierz Amarasinghe, Harindra H.E. Kadalayil, Latha Beattie, Alice Forster, Jade Blakemore, Stuart S.J. Parker, Helen Bryant, Dean Larrayoz, Marta Clifford, Ruth Robbe, Pauline Davis, Zadie Z.A. Else, Monica Howard, Dena D.R. Stamatopoulos, Basile Steele, Andrew Rosenquist, Richard Collins, Andrew Pettitt, Andrew A.R. Hillmen, Peter Plass, Christoph Schuh, Anna Catovsky, Daniel Oscier, David Graham Rose-Zerilli, Matthew M.J.J. Oakes, Christopher C.C. Strefford, Jonathan J.C. 2019-08-01 3 full-text file(s): application/pdf | application/pdf | application/pdf http://hdl.handle.net/2013/ULB-DIPOT:oai:dipot.ulb.ac.be:2013/296789 https://dipot.ulb.ac.be/dspace/bitstream/2013/296789/1/elsevier_280433.pdf https://dipot.ulb.ac.be/dspace/bitstream/2013/296789/4/doi_280433.pdf https://dipot.ulb.ac.be/dspace/bitstream/2013/296789/7/2019_Wojdacz.pdf en eng uri/info:doi/10.1182/bloodadvances.2019000237 uri/info:pmid/31434681 uri/info:scp/85071580517 https://dipot.ulb.ac.be/dspace/bitstream/2013/296789/1/elsevier_280433.pdf https://dipot.ulb.ac.be/dspace/bitstream/2013/296789/4/doi_280433.pdf https://dipot.ulb.ac.be/dspace/bitstream/2013/296789/7/2019_Wojdacz.pdf http://hdl.handle.net/2013/ULB-DIPOT:oai:dipot.ulb.ac.be:2013/296789 3 full-text file(s): info:eu-repo/semantics/restrictedAccess | info:eu-repo/semantics/restrictedAccess | info:eu-repo/semantics/openAccess Blood Advances, 3 (16 Généralités info:eu-repo/semantics/article info:ulb-repo/semantics/articlePeerReview info:ulb-repo/semantics/openurl/article 2019 ftunivbruxelles 2022-06-12T21:48:06Z 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 5 605) 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 5 245/305), 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 5 .018) in CLL4, and for progression-free survival (HR, 0.25; 95% CI, 0.10-0.57; P 5 .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. SCOPUS: ar.j info:eu-repo/semantics/published Article in Journal/Newspaper Arctic DI-fusion : dépôt institutionnel de l'Université libre de Bruxelles (ULB) Arctic |
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DI-fusion : dépôt institutionnel de l'Université libre de Bruxelles (ULB) |
op_collection_id |
ftunivbruxelles |
language |
English |
topic |
Généralités |
spellingShingle |
Généralités Wojdacz, Tomasz Kazimierz Amarasinghe, Harindra H.E. Kadalayil, Latha Beattie, Alice Forster, Jade Blakemore, Stuart S.J. Parker, Helen Bryant, Dean Larrayoz, Marta Clifford, Ruth Robbe, Pauline Davis, Zadie Z.A. Else, Monica Howard, Dena D.R. Stamatopoulos, Basile Steele, Andrew Rosenquist, Richard Collins, Andrew Pettitt, Andrew A.R. Hillmen, Peter Plass, Christoph Schuh, Anna Catovsky, Daniel Oscier, David Graham Rose-Zerilli, Matthew M.J.J. Oakes, Christopher C.C. Strefford, Jonathan J.C. Clinical significance of DNA methylation in chronic lymphocytic leukemia patients: Results from 3 UK clinical trials |
topic_facet |
Généralités |
description |
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 5 605) 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 5 245/305), 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 5 .018) in CLL4, and for progression-free survival (HR, 0.25; 95% CI, 0.10-0.57; P 5 .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. SCOPUS: ar.j info:eu-repo/semantics/published |
format |
Article in Journal/Newspaper |
author |
Wojdacz, Tomasz Kazimierz Amarasinghe, Harindra H.E. Kadalayil, Latha Beattie, Alice Forster, Jade Blakemore, Stuart S.J. Parker, Helen Bryant, Dean Larrayoz, Marta Clifford, Ruth Robbe, Pauline Davis, Zadie Z.A. Else, Monica Howard, Dena D.R. Stamatopoulos, Basile Steele, Andrew Rosenquist, Richard Collins, Andrew Pettitt, Andrew A.R. Hillmen, Peter Plass, Christoph Schuh, Anna Catovsky, Daniel Oscier, David Graham Rose-Zerilli, Matthew M.J.J. Oakes, Christopher C.C. Strefford, Jonathan J.C. |
author_facet |
Wojdacz, Tomasz Kazimierz Amarasinghe, Harindra H.E. Kadalayil, Latha Beattie, Alice Forster, Jade Blakemore, Stuart S.J. Parker, Helen Bryant, Dean Larrayoz, Marta Clifford, Ruth Robbe, Pauline Davis, Zadie Z.A. Else, Monica Howard, Dena D.R. Stamatopoulos, Basile Steele, Andrew Rosenquist, Richard Collins, Andrew Pettitt, Andrew A.R. Hillmen, Peter Plass, Christoph Schuh, Anna Catovsky, Daniel Oscier, David Graham Rose-Zerilli, Matthew M.J.J. Oakes, Christopher C.C. Strefford, Jonathan J.C. |
author_sort |
Wojdacz, Tomasz Kazimierz |
title |
Clinical significance of DNA methylation in chronic lymphocytic leukemia patients: Results from 3 UK clinical trials |
title_short |
Clinical significance of DNA methylation in chronic lymphocytic leukemia patients: Results from 3 UK clinical trials |
title_full |
Clinical significance of DNA methylation in chronic lymphocytic leukemia patients: Results from 3 UK clinical trials |
title_fullStr |
Clinical significance of DNA methylation in chronic lymphocytic leukemia patients: Results from 3 UK clinical trials |
title_full_unstemmed |
Clinical significance of DNA methylation in chronic lymphocytic leukemia patients: Results from 3 UK clinical trials |
title_sort |
clinical significance of dna methylation in chronic lymphocytic leukemia patients: results from 3 uk clinical trials |
publishDate |
2019 |
url |
http://hdl.handle.net/2013/ULB-DIPOT:oai:dipot.ulb.ac.be:2013/296789 https://dipot.ulb.ac.be/dspace/bitstream/2013/296789/1/elsevier_280433.pdf https://dipot.ulb.ac.be/dspace/bitstream/2013/296789/4/doi_280433.pdf https://dipot.ulb.ac.be/dspace/bitstream/2013/296789/7/2019_Wojdacz.pdf |
geographic |
Arctic |
geographic_facet |
Arctic |
genre |
Arctic |
genre_facet |
Arctic |
op_source |
Blood Advances, 3 (16 |
op_relation |
uri/info:doi/10.1182/bloodadvances.2019000237 uri/info:pmid/31434681 uri/info:scp/85071580517 https://dipot.ulb.ac.be/dspace/bitstream/2013/296789/1/elsevier_280433.pdf https://dipot.ulb.ac.be/dspace/bitstream/2013/296789/4/doi_280433.pdf https://dipot.ulb.ac.be/dspace/bitstream/2013/296789/7/2019_Wojdacz.pdf http://hdl.handle.net/2013/ULB-DIPOT:oai:dipot.ulb.ac.be:2013/296789 |
op_rights |
3 full-text file(s): info:eu-repo/semantics/restrictedAccess | info:eu-repo/semantics/restrictedAccess | info:eu-repo/semantics/openAccess |
_version_ |
1766342359090462720 |