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

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title = "Prognostic impact of epigenetic classification in chronic lymphocytic leukemia: The case of subset #2",
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), na{\"i}ve 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.",
keywords = "CLL, epigenetic classification, methylation, prognosis",
author = "Sujata Bhoi and Viktor Ljungstr{\"o}m and Panagiotis Baliakas and Mattias Mattsson and Smedby, {Karin E.} and Gunnar Juliusson and Richard Rosenquist and Larry Mansouri",
year = "2016",
month = "6",
day = "2",
doi = "10.1080/15592294.2016.1178432",
language = "English",
volume = "11",
pages = "449--455",
journal = "Epigenetics",
issn = "1559-2294",
publisher = "Landes Bioscience",
number = "6",