Universität zu Köln

Grimm, Christina ORCID: 0000-0002-4676-8870, Herling, Carmen Diana, Komnidi, Anastasia, Hussong, Michelle, Kreuzer, Karl-Anton, Hallek, Michael ORCID: 0000-0002-7425-4455 and Schweiger, Michal R. (2022). Evaluation of a Prognostic Epigenetic Classification System in Chronic Lymphocytic Leukemia Patients. Biomark. Insights, 17. LONDON: SAGE PUBLICATIONS LTD. ISSN 1177-2719

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Abstract

BACKGROUND: Methylation at 5 CpG sites was previously shown to classify chronic lymphocytic leukemia (CLL) into 3 prognostic subgroups. Here, we aimed to validate the marker set in an additional cohort and to evaluate its clinical utility for CLL patient stratification. METHODS: We evaluated this epigenetic marker set in 79 German patients using bisulfite treatment followed by pyrosequencing and classification using a support vector machine-learning tool. RESULTS: The n-CLL, i-CLL, and m-CLL classification was detected in 28 (35%). 10 (13%), and 41 (51%) patients, respectively. Epigenetic grouping was associated with IGHV mutational status (P=2 x 10(-12)), isolated del13q (P=9x 10(-6)), del17p (P= .015), complex karyotype (P= .005), VH-usage, and clinical outcome as time to first treatment (P= 1.4 x 10(-12)) and overall survival (P= .003). Multivariate Cox regression analysis identified n-CLL as a factor for earlier treatment hazard ratio (HR), 6.3 (95% confidence interval [CI] 2.4-16.4; P= .0002) compared to IGHV mutational status (HR 4.6, 95% CI 1.9-11.3, P= .0008). In addition, when comparing the prognostic value of the epigenetic classification system with the IGHV classification, epigenetic grouping performed better compared to IGHV mutational status using Kaplan-Meier estimation and allowed the identification of a third, intermediate (i-CLL) group. Thus, our study confirmed the prognostic value of the epigenetic marker set for patient stratification in routine clinical diagnostics.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Grimm, Christina UNSPECIFIED orcid.org/0000-0002-4676-8870 UNSPECIFIED Herling, Carmen Diana UNSPECIFIED UNSPECIFIED UNSPECIFIED Komnidi, Anastasia UNSPECIFIED UNSPECIFIED UNSPECIFIED Hussong, Michelle UNSPECIFIED UNSPECIFIED UNSPECIFIED Kreuzer, Karl-Anton UNSPECIFIED UNSPECIFIED UNSPECIFIED Hallek, Michael UNSPECIFIED orcid.org/0000-0002-7425-4455 UNSPECIFIED Schweiger, Michal R. UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-661457
DOI:	10.1177/11772719211067972
Journal or Publication Title:	Biomark. Insights
Volume:	17
Date:	2022
Publisher:	SAGE PUBLICATIONS LTD
Place of Publication:	LONDON
ISSN:	1177-2719
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language DNA METHYLATION Multiple languages Medicine, Research & Experimental Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/66145