Models for mature T-cell lymphomas—A critical appraisal of experimental systems and their contribution to current T-cell tumorigenic concepts

• Published in: Critical reviews in oncology/hematology Vol. 88; no. 3; pp. 680 - 695
• Main Authors: Warner, Kathrin, Crispatzu, Giuliano, Al-Ghaili, Nabil, Weit, Nicole, Florou, Vaia, You, M. James, Newrzela, Sebastian, Herling, Marco
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier Ireland Ltd 01-12-2013
• Subjects: Animals; Cell Line, Tumor; Cell Transformation, Neoplastic; Disease Models, Animal; Gene expression profiling in T-cell lymphoma; Hematology, Oncology and Palliative Medicine; Humans; Lymphoma modeling; Lymphoma, T-Cell - etiology; Lymphoma, T-Cell - pathology; Mature T-cell lymphoma/leukemia; Mice; Murine lymphoma classification; Neoplasm Grading; T-cell tumorigenesis; Murine lymphoma classification; Gene expression profiling in T-cell lymphoma; T-cell tumorigenesis; Mature T-cell lymphoma/leukemia; Lymphoma modeling
• ISSN: 1040-8428; 1879-0461
• DOI: 10.1016/j.critrevonc.2013.07.014

Abstract Mature T-cell lymphomas/leukemias (MTCL) have been understudied lymphoid neoplasms that currently receive growing attention. Our historically rudimentary molecular understanding and dissatisfactory interventional success in this complex and for the most part poor-prognostic group of tumors is only slightly improving. A major limiting aspect in further progress in these rare neoplasms is the lack of suitable model systems that would substantially facilitate pathogenic studies and pre-clinical drug evaluations. Such representations of MTCL have thus far not been systematically appraised. We therefore provide an overview on existing models and point out their particular advantages and limitations in the context of the specific scientific questions. After addressing issues of species-specific differences and classifications, we summarize data on MTCL cell lines of human as well as murine origin, on murine strain predispositions to MTCL, on available models of genetically engineered mice, and on transplant systems. From an in-silico meta-analysis of available primary data of gene expression profiles on human MTCL we cross-reference genes reported to transform T-cells in mice and reflect on their general vs entity-restricted relevance and on target-promoter influences. Overall, we identify the urgent need for new models of higher fidelity to human MTCL with respect to their increasingly recognized diversity and to predictions of drug response.