![[feed]](/style/images/feed-icon-14x14.png){kind=icon}
Tools
Tools
Preview |
PDF (Original Article)
- Requires a PDF viewer such as GSview, Xpdf or Adobe Acrobat Reader
2MB |
Preview |
PDF (Supplementary Appendix)
- Requires a PDF viewer such as GSview, Xpdf or Adobe Acrobat Reader
7MB |
| Item Type: | Article |
|---|---|
| Title: | Small molecule SUMO inhibition for biomarker-informed B-cell lymphoma therapy |
| Creators: |
Demel, U.M.  ORCID: https://orcid.org/0000-0002-6480-4185, Wirth, M. ORCID: https://orcid.org/0000-0002-8340-0872, Yousefian, S. ORCID: https://orcid.org/0000-0003-0902-0369, Zhang, L., Isaakidis, K., Dönig, J., Böger, M. ORCID: https://orcid.org/0000-0001-9301-5022, Singh, N., Köse, H., Haas, S. ORCID: https://orcid.org/0000-0001-9227-2051, Müller, S., Schick, M. ORCID: https://orcid.org/0009-0003-8626-0611 and Keller, U. ORCID: https://orcid.org/0000-0002-8485-1958
|
| 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 |
Repository Staff Only: item control page
