function in T‐cell development, the Setd2 cKO mice were generated with Lck‐Cre transgenic mice [47]. After comparing the proportion of intraepithelial T cells in Setd2 wild‐type versus deficient mice, they observed a significant increase in the population of γδ‐positive T cells in Setd2‐deficient mice. Although these mice do not perfectly recapitulate human EATL, this model may provide a very useful tool for future modeling of this fatal disease and is being evaluated in preclinical studies.
Conclusion
Over the years, murine models have played crucial roles as versatile tools for detailed investigation of T‐cell lymphomas. We now have a deeper understanding of the underlying mechanisms, disease pathogenesis and potential therapeutic interventions. Nevertheless, it is essential to understand the limitations of these model systems. Lack of precise simulation of the human disease and the microenvironment in mice are few among many shortcomings that hinder the success of novel drugs in clinical trials. The advent of targeted genetic manipulation using novel technologies may eventually resolve and refine the remaining differences making mouse the ultimate model organism of choice to study human ailments.
Must Reads
Sakata‐Yanagimoto, M., Enami, T., Yoshida, K., et al. (2014). Somatic RHOA mutation in angioimmunoblastic T cell lymphoma. Nat Genet 46 (2): 171–175.
Miething, C., Grundler, R., Fend F, et al. (2003). The oncogenic fusion protein nucleophosmin–anaplastic lymphoma kinase (NPM–ALK) induces two distinct malignant phenotypes in a murine retroviral transplantation model. Oncogene 22 (30): 4642–4647.
Chiarle, R., Gong, J.Z., Guasparri, I. et al. (2003). NPM‐ALK transgenic mice spontaneously develop T‐cell lymphomas and plasma cell tumors. Blood 101 (5): 1919–1927.
Kawano, N., Ishikawa, F., Shimoda, K. et al. (2005). Efficient engraftment of primary adult T‐cell leukemia cells in newborn NOD/SCID/beta2‐microglobulin(null) mice. Leukemia 19 (8): 1384–1390.
Cornejo, M.G., Kharas, M.G., Werneck, M.B. et al. (2009). Constitutive JAK3 activation induces lymphoproliferative syndromes in murine bone marrow transplantation models. Blood 113 (12): 2746–2754.
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