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Prognostic impact of epigenetic classification in chronic lymphocytic leukemia: The case of subset #2
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology. Uppsala University, Science for Life Laboratory, SciLifeLab.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology. Uppsala University, Science for Life Laboratory, SciLifeLab.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology. Uppsala University, Science for Life Laboratory, SciLifeLab.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology. Uppsala University, Science for Life Laboratory, SciLifeLab.
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2016 (English)In: Epigenetics, ISSN 1559-2294, E-ISSN 1559-2308, Vol. 11, no 6, 449-455 p.Article in journal (Refereed) Published
Abstract [en]

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), naive 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.

Place, publisher, year, edition, pages
2016. Vol. 11, no 6, 449-455 p.
Keyword [en]
CLL, epigenetic classification, methylation, prognosis
National Category
Cancer and Oncology Medical Genetics
Identifiers
URN: urn:nbn:se:uu:diva-303408DOI: 10.1080/15592294.2016.1178432ISI: 000380902700006PubMedID: 27128508OAI: oai:DiVA.org:uu-303408DiVA: diva2:971733
Funder
Swedish Cancer SocietySwedish Research Council
Available from: 2016-09-19 Created: 2016-09-19 Last updated: 2016-09-19Bibliographically approved

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Bhoi, SujataLjungström, ViktorBaliakas, PanagiotisMattsson, MattiasRosenquist, RichardMansouri, Larry
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Experimental and Clinical OncologyScience for Life Laboratory, SciLifeLab
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Epigenetics
Cancer and OncologyMedical Genetics

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