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

Research output: Contribution to journalArticle

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 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.

Details

Authors
  • Sujata Bhoi
  • Viktor Ljungström
  • Panagiotis Baliakas
  • Mattias Mattsson
  • Karin E. Smedby
  • Gunnar Juliusson
  • Richard Rosenquist
  • Larry Mansouri
Organisations
External organisations
  • Uppsala University
  • Karolinska Institutet
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Medical Genetics
  • Cancer and Oncology

Keywords

  • CLL, epigenetic classification, methylation, prognosis
Original languageEnglish
Pages (from-to)449-455
Number of pages7
JournalEpigenetics
Volume11
Issue number6
Publication statusPublished - 2016 Jun 2
Publication categoryResearch
Peer-reviewedYes