Xenograft models of chronic lymphocytic leukemia: problems, pitfalls and future directions

• Published in: Leukemia Vol. 27; no. 3; pp. 534 - 540
• Main Authors: Bertilaccio, M T S, Scielzo, C, Simonetti, G, Ten Hacken, E, Apollonio, B, Ghia, P, Caligaris-Cappio, F
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.03.2013; Nature Publishing Group
• Subjects: 631/67/1059/2325; 692/699/67/1990/283/1895; 692/700/565/545/576; Analysis; Animal experimentation; Animal models; Animals; Blood cancer; Cancer Research; Care and treatment; Cell lines; Cells; Chronic lymphocytic leukemia; Constraint modelling; Critical Care Medicine; Diabetes; Disease Models, Animal; Drug Evaluation, Preclinical; Drug testing; Health aspects; Hematology; Humans; Immunodeficiency; Immunoglobulins; Intensive; Internal Medicine; Kinases; Leukemia; Leukemia, Lymphocytic, Chronic, B-Cell - drug therapy; Leukemia, Lymphocytic, Chronic, B-Cell - etiology; Leukemia, Lymphocytic, Chronic, B-Cell - pathology; Lymphatic leukemia; Lymphocytes; Lymphoma; Medicine; Medicine & Public Health; Mice; Microenvironments; Mutation; Oncology; Pathogenesis; Physiological aspects; Radiation; review; Transplantation, Heterologous; Transplants & implants; Tumor cells; Tumors; Xenograft Model Antitumor Assays; Xenografts; Xenotransplantation; Italy; immunodeficient mice; primary CLL cells; CLL xenograft models; CLL cell lines
• ISSN: 0887-6924; 1476-5551
• DOI: 10.1038/leu.2012.268

Xenotransplantation of human tumor cells into immunodeficient mice has been a powerful preclinical tool in several hematological malignancies, with the notable exception of chronic lymphocytic leukemia (CLL). For several decades, this possibility was hampered by the inefficient and/or short-term engrafment of CLL cells into available animals. The development of new generations of immunocompromised mice has allowed to partially overcome these constraints. Novel humanized animal models have been created that allow to recapitulate the pathogenesis of the disease and the complex in vivo relationships between leukemic cells and the microenvironment. In this review we discuss the development of xenograft models of CLL, how they may help elucidating the mechanisms that account for the natural history of the disease and facilitating the design of novel therapeutic approaches.