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| Item Type: | Article |
|---|---|
| Title: | Small molecule SUMO inhibition for biomarker-informed B-cell lymphoma therapy |
| Creators Name: | Demel, U.M., Wirth, M., Yousefian, S., Zhang, L., Isaakidis, K., Dönig, J., Böger, M., Singh, N., Köse, H., Haas, S., Müller, S., 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, Animals, Mice |
| Source: | Haematologica |
| ISSN: | 0390-6078 |
| Publisher: | Ferrata Storti Foundation |
| Volume: | 108 |
| Number: | 2 |
| Page Range: | 555-567 |
| Date: | February 2023 |
| Official Publication: | https://doi.org/10.3324/haematol.2022.280995 |
| PubMed: | View item in PubMed |
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