Prognostic impact of epigenetic classification in chronic lymphocytic leukemia: The case of subset #2. Issue 6 (2nd June 2016)

• Record Type: Journal Article
• Authors: Bhoi, Sujata; Ljungström, Viktor; Baliakas, Panagiotis; Mattsson, Mattias; Smedby, Karin E.; Juliusson, Gunnar; Rosenquist, Richard; Mansouri, Larry
• Is Part Of: Epigenetics. Volume 11:Issue 6(2016)
• Page Start: 449
• Page End: 455
• Publication Date: 2016-06-02
• Subjects: CLL -- epigenetic classification -- methylation -- prognosis; Epigenesis -- Periodicals; Epigenetica; 572.86505
• DOI: 10.1080/15592294.2016.1178432
• Languages: English
• ISSNs: 1559-2294

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.