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.
本研究揭示了癌蛋白DEK在B细胞淋巴瘤中的关键作用。我们发现，在低级别B细胞淋巴瘤病例中，DEK表达与肿瘤增殖增强及总体生存率降低相关。同时，我们观察到DEK表达与LGBCL肿瘤的拷贝数变异存在显著关联，这为LGBCL的发病机制提供了新的解释路径，值得进一步探究。为探讨DEK在B细胞淋巴瘤中的机制性作用，我们构建了DEK敲除细胞系模型。该模型显示，DEK缺失会导致细胞增殖减缓，并改变关键细胞周期和凋亡相关蛋白（包括Bcl-2、Bcl-xL和p53）的表达。值得注意的是，DEK缺失细胞对凋亡诱导剂（如维奈托克和星形孢菌素）的敏感性增强，这凸显了靶向DEK在B细胞淋巴瘤治疗中的潜力。总之，我们的研究有助于更深入理解DEK作为癌蛋白在B细胞淋巴瘤中的作用，同时表明其既可成为有前景的治疗靶点，也可作为侵袭性LGBCL的新型生物标志物。进一步阐明DEK介导肿瘤发生的分子机制，或将为改善B细胞淋巴瘤患者的治疗策略和临床预后开辟新途径。
肿瘤(癌症)患者之家