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Clinical significan...
Clinical significance of DNA methylation in chronic lymphocytic leukemia patients: results from 3 UK clinical trials
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Wojdacz, TK (author)
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Amarasinghe, HE (author)
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Kadalayil, L (author)
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Beattie, A (author)
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Forster, J (author)
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Blakemore, SJ (author)
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Parker, H (author)
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Bryant, D (author)
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Larrayoz, M (author)
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Clifford, R (author)
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Robbe, P (author)
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Davis, ZA (author)
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Else, M (author)
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Howard, DR (author)
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Stamatopoulos, B (author)
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Steele, AJ (author)
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- Rosenquist, R (author)
- Karolinska Institutet
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Collins, A (author)
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Pettitt, AR (author)
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Hillmen, P (author)
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Plass, C (author)
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Schuh, A (author)
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Catovsky, D (author)
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Oscier, DG (author)
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Rose-Zerilli, MJJ (author)
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Oakes, CC (author)
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Strefford, JC (author)
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(creator_code:org_t)
- 2019-08-21
- 2019
- English.
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In: Blood advances. - : American Society of Hematology. - 2473-9537 .- 2473-9529. ; 3:16, s. 2474-2481
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Abstract
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- 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.
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- ref (subject category)
- art (subject category)
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To the university's database
- By the author/editor
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Wojdacz, TK
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Amarasinghe, HE
-
Kadalayil, L
-
Beattie, A
-
Forster, J
-
Blakemore, SJ
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show more...
-
Parker, H
-
Bryant, D
-
Larrayoz, M
-
Clifford, R
-
Robbe, P
-
Davis, ZA
-
Else, M
-
Howard, DR
-
Stamatopoulos, B
-
Steele, AJ
-
Rosenquist, R
-
Collins, A
-
Pettitt, AR
-
Hillmen, P
-
Plass, C
-
Schuh, A
-
Catovsky, D
-
Oscier, DG
-
Rose-Zerilli, MJ ...
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Oakes, CC
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Strefford, JC
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show less...
- Articles in the publication
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Blood advances
- By the university
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Karolinska Institutet