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Updated: Aug 28, 2025
Localization of SUMO-modified Proteins Using Fluorescent Sumo-trapping Proteins
Published on: April 27, 2019
Small-molecule SUMO inhibition for biomarker-informed B-cell lymphoma therapy
Uta M Demel1, Matthias Wirth2, Schayan Yousefian3
1Department of Hematology, Oncology and Cancer Immunology, Campus Benjamin Franklin, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, 12203 Berlin, Germany; Max-Delbrück-Center for Molecular Medicine, 13125 Berlin, Germany; Clinician Scientist Program, Berlin Institute of Health (BIH), Berlin.
Abstract:
Aberrant activity of the SUMOylation pathway has been associated with MYC overexpression and poor prognosis in aggressive B-cell lymphoma (BCL) and other malignancies. Recently developed small-molecule inhibitors of SUMOylation (SUMOi) target the heterodimeric E1 SUMO activation complex (SAE1/UBA2). Here, we report that activated MYC signaling is an actionable molecular vulnerability in vitro and in a preclinical murine in vivo model of MYC-driven BCL. While SUMOi conferred direct effects on MYC-driven lymphoma cells, SUMO inhibition also resulted in substantial remodeling of various subsets of the innate and specific immunity in vivo. Specifically, SUMOi increased the number of memory B cells as well as cytotoxic and memory T cells, subsets that are attributed a key role within a coordinated anti-tumor immune response. In summary, our data constitute pharmacologic SUMOi as a powerful therapy in a subset of BCL causing massive remodeling of the normal B-cell and T-cell compartment.
