Journal article
U. Demel, Matthias Wirth, S. Yousefian, Le Zhang, Konstandina Isaakidis, Judith Dönig, Marlitt Böger, Nikita Singh, Hazal Köse, S. Haas, S. Müller, M. Schick, U. Keller
Haematologica, 2022
Haematologica, 2022
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APA
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Demel, U., Wirth, M., Yousefian, S., Zhang, L., Isaakidis, K., Dönig, J., … Keller, U. (2022). Small-molecule SUMO inhibition for biomarker-informed B-cell lymphoma therapy. Haematologica.
Chicago/Turabian
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Demel, U., Matthias Wirth, S. Yousefian, Le Zhang, Konstandina Isaakidis, Judith Dönig, Marlitt Böger, et al. “Small-Molecule SUMO Inhibition for Biomarker-Informed B-Cell Lymphoma Therapy.” Haematologica (2022).
MLA
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Demel, U., et al. “Small-Molecule SUMO Inhibition for Biomarker-Informed B-Cell Lymphoma Therapy.” Haematologica, 2022.
BibTeX Click to copy
@article{u2022a,
title = {Small-molecule SUMO inhibition for biomarker-informed B-cell lymphoma therapy},
year = {2022},
journal = {Haematologica},
author = {Demel, U. and Wirth, Matthias and Yousefian, S. and Zhang, Le and Isaakidis, Konstandina and Dönig, Judith and Böger, Marlitt and Singh, Nikita and Köse, Hazal and Haas, S. and Müller, S. and Schick, M. and Keller, U.}
}
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.