Evaluation of a Prognostic Epigenetic Classification System in Chronic Lymphocytic Leukemia Patients

Autor: Christina Grimm, Carmen Diana Herling, Anastasia Komnidi, Michelle Hussong, Karl-Anton Kreuzer, Michael Hallek, Michal R. Schweiger
Jazyk: angličtina
Rok vydání: 2022
Předmět:
Zdroj: Biomarker Insights, Vol 17 (2022)
Druh dokumentu: article
ISSN: 1177-2719
11772719
DOI: 10.1177/11772719211067972
Popis: 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 × 10 −12 ), isolated del13q ( P = 9 × 10 −6 ), del17p ( P = .015), complex karyotype ( P = .005), VH-usage, and clinical outcome as time to first treatment ( P = 1.4 × 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.
Databáze: Directory of Open Access Journals
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