IGHV@
慢性淋巴细胞白血病
表观遗传学
肿瘤科
生物
三体
蛋白质组学
白血病
生物信息学
免疫学
内科学
医学
遗传学
基因
作者
Anneke D. van Dijk,Tiara Griffen,Yihua Qiu,Fieke W. Hoff,Endurance Toro,Kevin Ruiz,Peter P. Ruvolo,James W. Lillard,Eveline S.J.M. de Bont,Jan A. Burger,William G. Wierda,Steven M. Kornblau
出处
期刊:Leukemia
[Springer Nature]
日期:2021-10-08
卷期号:36 (3): 712-722
被引量:4
标识
DOI:10.1038/s41375-021-01438-4
摘要
The chronic lymphocytic leukemia (CLL) armamentarium has evolved significantly, with novel therapies that inhibit Bruton Tyrosine Kinase, PI3K delta and/or the BCL2 protein improving outcomes. Still, the clinical course of CLL patients is highly variable and most previously recognized prognostic features lack the capacity to predict response to modern treatments indicating the need for new prognostic markers. In this study, we identified four epigenetically distinct proteomic signatures of a large cohort of CLL and related diseases derived samples (n = 871) using reverse phase protein array technology. These signatures are associated with clinical features including age, cytogenetic abnormalities [trisomy 12, del(13q) and del(17p)], immunoglobulin heavy-chain locus (IGHV) mutational load, ZAP-70 status, Binet and Rai staging as well as with the outcome measures of time to treatment and overall survival. Protein signature membership was identified as predictive marker for overall survival regardless of other clinical features. Among the analyzed epigenetic proteins, EZH2, HDAC6, and loss of H3K27me3 levels were the most independently associated with poor survival. These findings demonstrate that proteomic based epigenetic biomarkers can be used to better classify CLL patients and provide therapeutic guidance.
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