Clinical significance of DNA methylation in chronic lymphocytic leukemia patients: Results from 3 UK clinical trials
Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaper › Journal article › Research › peer-review
Links
- https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6712529/pdf/advancesADV2019000237.pdf
Final published version
DOI
- https://doi.org/10.1182/bloodadvances.2019000237
Final published version
- Tomasz K. Wojdacz
- Harindra E. Amarasinghe, University of Southampton ,
- Latha Kadalayil, University of Southampton ,
- Alice Beattie, University of Southampton ,
- Jade Forster, University of Southampton ,
- Stuart J. Blakemore, University of Southampton, University of Cologne ,
- Helen Parker, University of Southampton ,
- Dean Bryant, University of Southampton ,
- Marta Larrayoz, University of Southampton, University of Navarra ,
- Ruth Clifford, Oxford University, Oxford, UK. ,
- Pauline Robbe, Oxford University, Oxford, UK. ,
- Zadie A. Davis, The Royal Bournemouth and Christchurch Hospitals NHS Foundation Trust ,
- Monica Else, Institute of Cancer Research ,
- Dena R. Howard, Leeds University ,
- Basile Stamatopoulos, Université Libre de Bruxelles ,
- Andrew J. Steele, University of Southampton ,
- Richard Rosenquist, Karolinska Institutet ,
- Andrew Collins, University of Southampton ,
- Andrew R. Pettitt, University of Liverpool ,
- Peter Hillmen, Leeds University ,
- Christoph Plass, German Cancer Research Center, Heidelberg ,
- Anna Schuh, Oxford University, Oxford, UK. ,
- Daniel Catovsky, Institute of Cancer Research ,
- David G. Oscier, The Royal Bournemouth and Christchurch Hospitals NHS Foundation Trust ,
- Matthew J.J. Rose-Zerilli, University of Southampton ,
- Christopher C. Oakes, The Ohio State University ,
- Jonathan C. Strefford, University of Southampton
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.
| Original language | English |
|---|---|
| Journal | Blood Advances |
| Volume | 3 |
| Issue | 16 |
| Pages (from-to) | 2474-2481 |
| Number of pages | 8 |
| ISSN | 2473-9529 |
| DOIs | |
| Publication status | Published - 27 Aug 2019 |
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