慢性淋巴细胞白血病患者预后表观遗传分类系统的评价。

IF 3.4 Q2 MEDICINE, RESEARCH & EXPERIMENTAL Biomarker Insights Pub Date : 2022-01-19 eCollection Date: 2022-01-01 DOI:10.1177/11772719211067972

Christina Grimm, Carmen Diana Herling, Anastasia Komnidi, Michelle Hussong, Karl-Anton Kreuzer, Michael Hallek, Michal R Schweiger

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引用次数: 2

摘要

背景:5个CpG位点的甲基化先前被证明可以将慢性淋巴细胞白血病(CLL)分为3个预后亚组。在这里，我们的目的是在另一个队列中验证该标记集，并评估其在CLL患者分层中的临床应用。方法:我们在79名德国患者中使用亚硫酸氢盐治疗，然后使用焦磷酸测序和使用支持向量机器学习工具进行分类，评估了这一表观遗传标记集。结果:n-CLL、i-CLL和m-CLL分型分别为28例(35%)、10例(13%)和41例(51%)。表观遗传分组与IGHV突变状态(P = 2 × 10-12)、分离del13q (P = 9 × 10-6)、del17p (P = 0.015)、复杂核型(P = 0.005)、vh使用、临床转归(P = 1.4 × 10-12)和总生存期(P = 0.003)相关。多因素Cox回归分析发现，n-CLL是早期治疗风险比(HR)的一个因素，为6.3(95%可信区间[CI] 2.4-16.4;P = 0.0002)与IGHV突变状态相比(HR 4.6, 95% CI 1.9-11.3, P = 0.0008)。此外，当比较表观遗传分类系统与IGHV分类的预后价值时，使用Kaplan-Meier估计，表观遗传分组比IGHV突变状态表现更好，并允许识别第三个中间(i-CLL)组。因此，我们的研究证实了表观遗传标记在常规临床诊断中对患者分层的预后价值。

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

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.