DEK regulates B-cell proliferative capacity and is associated with aggressive disease in low-grade B-cell lymphomas

• Published in: Blood cancer journal (New York) Vol. 14; no. 1; pp. 172 - 10
• Main Authors: Hopper, Melissa A., Dropik, Abigail R., Walker, Janek S., Novak, Joseph P., Laverty, Miranda S., Manske, Michelle K., Wu, Xiaosheng, Wenzl, Kerstin, Krull, Jordan E., Sarangi, Vivekananda, Maurer, Matthew J., Yang, Zhi-Zhang, Del Busso, Miles D., Habermann, Thomas M., Link, Brian K., Rimsza, Lisa M., Witzig, Thomas E., Ansell, Stephen M., Cerhan, James R., Jevremovic, Dragan, Novak, Anne J.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 09.10.2024; Springer Nature B.V; Nature Publishing Group
• Subjects: 13/109; 13/2; 13/31; 13/89; 14/1; 14/19; 38/23; 38/39; 42; 45; 45/91; 631/67/1990/291/1621/1915; 631/67/395; 631/67/69; Apoptosis; B-Lymphocytes - metabolism; B-Lymphocytes - pathology; Biomedical and Life Sciences; Biomedicine; Cancer Research; Cell cycle; Cell Line, Tumor; Cell Proliferation; Chromosomal Proteins, Non-Histone - genetics; Chromosomal Proteins, Non-Histone - metabolism; Female; Gene Expression Regulation, Neoplastic; Hematology; Humans; Lymphoma; Lymphoma, B-Cell - genetics; Lymphoma, B-Cell - metabolism; Lymphoma, B-Cell - pathology; Male; Neoplasm Grading; Oncogene Proteins - genetics; Oncogene Proteins - metabolism; Oncology; Poly-ADP-Ribose Binding Proteins - genetics; Poly-ADP-Ribose Binding Proteins - metabolism
• ISSN: 2044-5385; 2044-5385
• DOI: 10.1038/s41408-024-01145-0

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.