RPPA-based proteomics recognizes distinct epigenetic signatures in chronic lymphocytic leukemia with clinical consequences

Anneke D van Dijk*, Ti'ara L Griffen, Yihua H Qiu, Fieke W Hoff, Endurance Toro, Kevin Ruiz, Peter P Ruvolo, James W Lillard, Eveline S J M de Bont, Jan A Burger, William Wierda, Steven M Kornblau

*Bijbehorende auteur voor dit werk

    OnderzoeksoutputAcademicpeer review

    5 Citaten (Scopus)
    104 Downloads (Pure)


    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.

    Originele taal-2English
    Pagina's (van-tot)712–722
    Aantal pagina's11
    Vroegere onlinedatum8-okt.-2021
    StatusPublished - mrt.-2022


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