Dek-KO Mouse

DEK, a highly conserved nuclear factor, is an oncogene [5,8]. It was initially discovered as fused with the NUP214 gene in some acute myeloid leukemia patients, forming the DEK-NUP214 oncoprotein [5,8,9]. DEK is highly expressed in most human tissues and overexpressed in numerous cancers, and is involved in epigenetic and transcriptional regulation, as well as multiple cellular processes like self-renewal, proliferation, differentiation, senescence, and apoptosis [8]. Secreted DEK can act as a hematopoietic cytokine, regulating hematopoiesis by activating signaling through the CXCL2 receptor, enhancing hematopoietic stem cell proliferation and reducing hematopoietic progenitor cell numbers [7].

In the context of head and neck carcinomas, a novel DEK::AFF2 fusion carcinoma has been described. These tumors occur in multiple head and neck sites, show aggressive behavior with local recurrence, lymph node, and distant metastasis [1,2,3,6]. In sinonasal and skull base non-keratinizing squamous cell carcinomas, RNA sequencing identified DEK-AFF2 fusions in a significant proportion of cases. Histologically, they have distinct features and overlap with some benign and malignant tumors, but are confirmed as aggressive malignancies despite their relatively bland histology [2]. In squamous cell carcinoma (SCC), DEK plays important roles in disease progression and is a potential therapeutic target, especially for HPV-associated SCC, though the mechanism remains unclear [5]. In asthma, DEK deficiency alleviates airway inflammation by down-regulating PINK1-Parkin mitophagy, NLRP3 inflammasome activation, and apoptosis, likely through the DEK/ATAD3A/DRP1 signaling axis [4].

In summary, DEK is an oncogene involved in diverse biological processes and disease conditions. Its role in diseases such as leukemia, head and neck carcinomas, SCC, and asthma has been revealed through various studies. Understanding DEK's functions, especially through gene-knockout or conditional-knockout models as in the asthma study [4], can provide insights into disease mechanisms and potential therapeutic targets.

References:

1. Ruangritchankul, Komkrit, Sandison, Ann. 2022. DEK::AFF2 Fusion Carcinomas of Head and Neck. In Advances in anatomic pathology, 30, 86-94. doi:10.1097/PAP.0000000000000376. https://pubmed.ncbi.nlm.nih.gov/36221219/

2. Rooper, Lisa M, Agaimy, Abbas, Dickson, Brendan C, Weinreb, Ilan, Bishop, Justin A. . DEK-AFF2 Carcinoma of the Sinonasal Region and Skull Base: Detailed Clinicopathologic Characterization of a Distinctive Entity. In The American journal of surgical pathology, 45, 1682-1693. doi:10.1097/PAS.0000000000001741. https://pubmed.ncbi.nlm.nih.gov/34049316/

3. Amin, Sara E, Lewis, James S, Bridge, Julia A, Bishop, Justin A, Saluja, Karan. 2024. DEK::AFF2 Fusion-Associated Squamous Cell Carcinoma: A Case Series with Literature Review on an Emerging and Challenging Entity. In Head and neck pathology, 18, 86. doi:10.1007/s12105-024-01690-x. https://pubmed.ncbi.nlm.nih.gov/39312022/

4. Bai, Qiaoyun, Liu, Ruobai, Quan, Changlin, Song, Yilan, Yan, Guanghai. 2024. DEK deficiency suppresses mitophagy to protect against house dust mite-induced asthma. In Frontiers in immunology, 14, 1289774. doi:10.3389/fimmu.2023.1289774. https://pubmed.ncbi.nlm.nih.gov/38274803/

5. Ishida, Kazuhisa, Nakashima, Takayuki, Shibata, Toshiyuki, Hara, Akira, Tomita, Hiroyuki. 2020. Role of the DEK oncogene in the development of squamous cell carcinoma. In International journal of clinical oncology, 25, 1563-1569. doi:10.1007/s10147-020-01735-5. https://pubmed.ncbi.nlm.nih.gov/32656741/

6. Rivera, Jonathan P, Kuo, Ying-Ju, Hang, Jen-Fan. 2024. DEK::AFF2 Carcinoma of the Sinonasal Tract and Skull Base: A Comprehensive Review. In Surgical pathology clinics, 17, 587-597. doi:10.1016/j.path.2024.07.008. https://pubmed.ncbi.nlm.nih.gov/39489551/

7. Bodine, David M. 2019. All hands on DEK. In The Journal of clinical investigation, 129, 2205-2206. doi:10.1172/JCI128986. https://pubmed.ncbi.nlm.nih.gov/31107244/

8. Sandén, C, Gullberg, U. 2015. The DEK oncoprotein and its emerging roles in gene regulation. In Leukemia, 29, 1632-6. doi:10.1038/leu.2015.72. https://pubmed.ncbi.nlm.nih.gov/25765544/

9. Panagopoulos, Ioannis, Gorunova, Ludmila, Torkildsen, Synne, Micci, Francesca, Heim, Sverre. . DEK-NUP214-Fusion Identified by RNA-Sequencing of an Acute Myeloid Leukemia with t(9;12)(q34;q15). In Cancer genomics & proteomics, 14, 437-443. doi:. https://pubmed.ncbi.nlm.nih.gov/29109093/