Prognostic impact of epigenetic classification in chronic lymphocytic leukemia : The case of subset #2
(2016) In Epigenetics 11(6). p.449-455- Abstract
ABSTRACT: Based on the methylation status of 5 single CpG sites, a novel epigenetic classification of chronic lymphocytic leukemia (CLL) was recently proposed, classifying CLL patients into 3 clinico-biological subgroups with different outcome, termed memory like CLL (m-CLL), naïve like CLL (n-CLL), and a third intermediate CLL subgroup (i-CLL). While m-CLL and n-CLL patients at large corresponded to patients carrying mutated and unmutated IGHV genes, respectively, limited information exists regarding the less defined i-CLL group. Using pyrosequencing, we investigated the prognostic impact of the proposed 5 CpG signature in a well-characterized CLL cohort (135 cases), including IGHV-mutated and unmutated patients as well as clinically... (More)
ABSTRACT: Based on the methylation status of 5 single CpG sites, a novel epigenetic classification of chronic lymphocytic leukemia (CLL) was recently proposed, classifying CLL patients into 3 clinico-biological subgroups with different outcome, termed memory like CLL (m-CLL), naïve like CLL (n-CLL), and a third intermediate CLL subgroup (i-CLL). While m-CLL and n-CLL patients at large corresponded to patients carrying mutated and unmutated IGHV genes, respectively, limited information exists regarding the less defined i-CLL group. Using pyrosequencing, we investigated the prognostic impact of the proposed 5 CpG signature in a well-characterized CLL cohort (135 cases), including IGHV-mutated and unmutated patients as well as clinically aggressive stereotyped subset #2 patients. Overall, we confirmed the signature's association with established prognostic markers. Moreover, in the presence of the IGHV mutational status, the epigenetic signature remained independently associated with both time-to-first-treatment and overall survival in multivariate analyses. As a prime finding, we observed that subset #2 patients were predominantly classified as i-CLL, probably reflecting their borderline IGHV mutational status (97–99% germline identity), though having a similarly poor prognosis as n-CLL patients. In summary, we validated the epigenetic classifier as an independent factor in CLL prognostication and provide further evidence that subset #2 is a member of the i-CLL group, hence supporting the existence of a third, intermediate epigenetic subgroup.
(Less)
- author
- Bhoi, Sujata ; Ljungström, Viktor ; Baliakas, Panagiotis ; Mattsson, Mattias ; Smedby, Karin E. ; Juliusson, Gunnar LU ; Rosenquist, Richard and Mansouri, Larry
- organization
- publishing date
- 2016-06-02
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- CLL, epigenetic classification, methylation, prognosis
- in
- Epigenetics
- volume
- 11
- issue
- 6
- pages
- 7 pages
- publisher
- Landes Bioscience
- external identifiers
-
- scopus:84973167177
- pmid:27128508
- wos:000380902700006
- ISSN
- 1559-2294
- DOI
- 10.1080/15592294.2016.1178432
- language
- English
- LU publication?
- yes
- id
- d38c2cc8-b5fa-4028-a376-7eaeb571c989
- date added to LUP
- 2017-01-25 13:06:46
- date last changed
- 2024-06-14 22:54:47
@article{d38c2cc8-b5fa-4028-a376-7eaeb571c989,
abstract = {{<p>ABSTRACT: Based on the methylation status of 5 single CpG sites, a novel epigenetic classification of chronic lymphocytic leukemia (CLL) was recently proposed, classifying CLL patients into 3 clinico-biological subgroups with different outcome, termed memory like CLL (m-CLL), naïve like CLL (n-CLL), and a third intermediate CLL subgroup (i-CLL). While m-CLL and n-CLL patients at large corresponded to patients carrying mutated and unmutated IGHV genes, respectively, limited information exists regarding the less defined i-CLL group. Using pyrosequencing, we investigated the prognostic impact of the proposed 5 CpG signature in a well-characterized CLL cohort (135 cases), including IGHV-mutated and unmutated patients as well as clinically aggressive stereotyped subset #2 patients. Overall, we confirmed the signature's association with established prognostic markers. Moreover, in the presence of the IGHV mutational status, the epigenetic signature remained independently associated with both time-to-first-treatment and overall survival in multivariate analyses. As a prime finding, we observed that subset #2 patients were predominantly classified as i-CLL, probably reflecting their borderline IGHV mutational status (97–99% germline identity), though having a similarly poor prognosis as n-CLL patients. In summary, we validated the epigenetic classifier as an independent factor in CLL prognostication and provide further evidence that subset #2 is a member of the i-CLL group, hence supporting the existence of a third, intermediate epigenetic subgroup.</p>}},
author = {{Bhoi, Sujata and Ljungström, Viktor and Baliakas, Panagiotis and Mattsson, Mattias and Smedby, Karin E. and Juliusson, Gunnar and Rosenquist, Richard and Mansouri, Larry}},
issn = {{1559-2294}},
keywords = {{CLL; epigenetic classification; methylation; prognosis}},
language = {{eng}},
month = {{06}},
number = {{6}},
pages = {{449--455}},
publisher = {{Landes Bioscience}},
series = {{Epigenetics}},
title = {{Prognostic impact of epigenetic classification in chronic lymphocytic leukemia : The case of subset #2}},
url = {{http://dx.doi.org/10.1080/15592294.2016.1178432}},
doi = {{10.1080/15592294.2016.1178432}},
volume = {{11}},
year = {{2016}},
}