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Small molecule SUMO inhibition for biomarker-informed B-cell lymphoma therapy

Item Type:Article
Title:Small molecule SUMO inhibition for biomarker-informed B-cell lymphoma therapy
Creators Name:Demel, U.M. and Wirth, M. and Yousefian, S. and Zhang, L. and Isaakidis, K. and Dönig, J. and Böger, M. and Singh, N. and Köse, H. 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 pre-clinical murine in vivo model of MYCdriven 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 antitumor immune response. In summary, our data constitute pharmacologic SUMOi as a powerful therapy in a subset of B-cell lymphomas causing massive remodeling of the normal B-cell and T-cell compartment.
Keywords:SUMO, MYC, B-Cell Lymphoma, Immune Activation
Publisher:Ferrata Storti Foundation
Date:22 September 2022
Official Publication:https://doi.org/10.3324/haematol.2022.280995
PubMed:View item in PubMed

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