DEK regulates B-cell proliferative capacity and is associated with aggressive disease in low-grade B-cell lymphomas
This study sheds light on the pivotal role of the oncoprotein DEK in B-cell lymphoma. We reveal DEK expression correlates with increased tumor proliferation and inferior overall survival in cases diagnosed with low-grade B-cell lymphoma (LGBCL). We also found significant correlation between DEK expression and copy number alterations in LGBCL tumors, highlighting a novel mechanism of LGBCL pathogenesis that warrants additional exploration. To interrogate the mechanistic role of DEK in B-cell lymphoma, we generated a DEK knockout cell line model, which demonstrated DEK depletion caused reduced proliferation and altered expression of key cell cycle and apoptosis-related proteins, including Bcl-2, Bcl-xL, and p53. Notably, DEK depleted cells showed increased sensitivity to apoptosis-inducing agents, including venetoclax and staurosporine, which underscores the therapeutic potential of targeting DEK in B-cell lymphomas. Overall, our study contributes to a better understanding of DEK's role as an oncoprotein in B-cell lymphomas, highlighting its potential as both a promising therapeutic target and a novel biomarker for aggressive LGBCL. Further research elucidating the molecular mechanisms underlying DEK-mediated tumorigenesis could pave the way for improved treatment strategies and better clinical outcomes for patients with B-cell lymphoma.
Authors
- Kerstin Wenzl (ORCID: https://orcid.org/0000-0002-3363-1795)
- Xiaosheng Wu (ORCID: https://orcid.org/0000-0001-8043-2177)
- Lisa M. Rimsza (ORCID: https://orcid.org/0000-0003-1268-2750)
- Jordan E. Krull (ORCID: https://orcid.org/0000-0001-6507-8085)
- Vivekananda Sarangi
- Dragan Jevremović (ORCID: https://orcid.org/0000-0002-1792-5822)
- Joseph P. Novak (ORCID: https://orcid.org/0000-0001-5676-6118)
- Thomas Matthew Habermann (ORCID: https://orcid.org/0000-0003-3532-9132)
- Anne J. Novak (ORCID: https://orcid.org/0000-0002-7904-1651)
- Michelle K. Manske (ORCID: https://orcid.org/0000-0002-4084-8351)
- Abigail R. Dropik (ORCID: https://orcid.org/0000-0002-7543-5768)
- Matthew J. Maurer (ORCID: https://orcid.org/0000-0002-1867-0526)
- Stephen M. Ansell (ORCID: https://orcid.org/0000-0003-1244-6758)
- Janek S. Walker (ORCID: https://orcid.org/0000-0002-2049-1527)
- Zhi-Zhang Yang (ORCID: https://orcid.org/0000-0002-1468-2300)
- Melissa A. Hopper (ORCID: https://orcid.org/0000-0003-0675-8253)
- James R. Cerhan (ORCID: https://orcid.org/0000-0002-7482-178X)
- Brian K. Link
- Thomas E. Witzig
- M. Laverty
- Miles Del Busso
Institutions
- University of Iowa (US)
- Mayo Clinic in Arizona (US)
- Mayo Clinic Hospital (US)
- Mayo Clinic in Florida (US)
Publication Details
- Journal
- Blood Cancer Journal
- Published
- 2024-10-09
- DOI
- https://doi.org/10.1038/s41408-024-01145-0
- Citations
- 3
- Primary Topic
- Nuclear Structure and Function
- Type
- article
- Field-Weighted Citation Impact
- 0.70
Funders
- National Institutes of Health
- National Cancer Institute
- National Institute of Allergy and Infectious Diseases