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Prognostic impact of epigenetic classification in chronic lymphocytic leukemia : The case of subset #2

Bhoi, Sujata; Ljungström, Viktor; Baliakas, Panagiotis; Mattsson, Mattias; Smedby, Karin E.; Juliusson, Gunnar LU ; Rosenquist, Richard and Mansouri, Larry (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.

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author
organization
publishing date
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
  • 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
2017-09-18 11:33:53
@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},
  keyword      = {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},
  volume       = {11},
  year         = {2016},
}