Clinical significance of DNA methylation in chronic lymphocytic leukemia patients: results from 3 UK clinical trials.
Adult
Aged
Aged, 80 and over
Chromosome Aberrations
Computational Biology
/ methods
DNA Methylation
Epigenesis, Genetic
Epigenomics
/ methods
Female
Gene Expression Profiling
Gene Expression Regulation, Leukemic
Humans
Immunoglobulin Heavy Chains
/ genetics
Leukemia, Lymphocytic, Chronic, B-Cell
/ diagnosis
Male
Middle Aged
Mutation
Neoplasm Staging
Prognosis
Proportional Hazards Models
Journal
Blood advances
ISSN: 2473-9537
Titre abrégé: Blood Adv
Pays: United States
ID NLM: 101698425
Informations de publication
Date de publication:
27 08 2019
27 08 2019
Historique:
received:
01
04
2019
accepted:
15
06
2019
entrez:
23
8
2019
pubmed:
23
8
2019
medline:
18
8
2020
Statut:
ppublish
Résumé
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;
Identifiants
pubmed: 31434681
pii: bloodadvances.2019000237
doi: 10.1182/bloodadvances.2019000237
pmc: PMC6712529
doi:
Substances chimiques
Immunoglobulin Heavy Chains
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
2474-2481Subventions
Organisme : Department of Health
ID : 07/01/38
Pays : United Kingdom
Organisme : Cancer Research UK
ID : C34999/A18087
Pays : United Kingdom
Organisme : Cancer Research UK
ID : C24563/A15581
Pays : United Kingdom
Informations de copyright
© 2019 by The American Society of Hematology.
Références
Leukemia. 2007 Jan;21(1):102-9
pubmed: 17082778
Lancet. 2007 Jul 21;370(9583):230-239
pubmed: 17658394
Lancet. 2010 Oct 2;376(9747):1164-74
pubmed: 20888994
J Clin Oncol. 2011 Jun 1;29(16):2223-9
pubmed: 21483000
Nat Genet. 2012 Nov;44(11):1236-42
pubmed: 23064414
Blood. 2013 Jan 17;121(3):468-75
pubmed: 23086750
Leukemia. 2013 Nov;27(11):2196-9
pubmed: 23558524
Haematologica. 2014 Apr;99(4):736-42
pubmed: 24584352
Leukemia. 2015 Mar;29(3):598-605
pubmed: 25151957
Nat Methods. 2014 Nov;11(11):1138-1140
pubmed: 25262207
Blood. 2014 Nov 13;124(20):3059-64
pubmed: 25281606
Leukemia. 2015 Dec;29(12):2411-4
pubmed: 26256637
Blood. 2015 Oct 15;126(16):1921-4
pubmed: 26276669
Nature. 2015 Oct 22;526(7574):525-30
pubmed: 26466571
Blood. 2016 Jan 14;127(2):208-15
pubmed: 26486789
Blood. 2016 Jan 21;127(3):303-9
pubmed: 26492934
Nat Genet. 2016 Mar;48(3):253-64
pubmed: 26780610
Epigenetics. 2016 Jun 2;11(6):449-55
pubmed: 27128508
Leukemia. 2017 Feb;31(2):510-514
pubmed: 27773930
Leukemia. 2017 Oct;31(10):2085-2093
pubmed: 28216660
Leukemia. 2017 Nov;31(11):2416-2425
pubmed: 28336937
Blood. 2017 Nov 23;130(21):2278-2282
pubmed: 29025740
Br J Haematol. 2018 Jan;180(1):33-40
pubmed: 29164608
Nat Med. 2018 Jun;24(6):868-880
pubmed: 29785028
Clin Cancer Res. 2018 Oct 15;24(20):5048-5057
pubmed: 29945996
N Engl J Med. 2018 Dec 27;379(26):2517-2528
pubmed: 30501481
Blood. 2019 May 9;133(19):2031-2042
pubmed: 30842083