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

Abstract

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.

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Acknowledgements

This project was supported by Associazione Italiana per la Ricerca sul Cancro (AIRC; Investigator Grant to PG and Special Program Molecular Clinical Oncology—5 per mille #9965 to PG and FC-C), Milano, Italy; ‘Fondazione Piera, Pietro e Giovanni Ferrero’, Alba, Italy; Fondazione CARIPLO, Milano, Italy; ‘CLLGRF—U.S./European Alliance for the Therapy of CLL’, FIRB and PRIN—Ministero Istruzione, Università e Ricerca (MIUR), Roma, Progetti Integrati Oncologia (PIO) e Progetto Finalizzato 2010—Ministero della Salute, Roma. CS is supported by the EHA Fellowship Program (2009/18). Figure was produced using Servier Medical Art: www.servier.com.

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Bertilaccio, M., Scielzo, C., Simonetti, G. et al. Xenograft models of chronic lymphocytic leukemia: problems, pitfalls and future directions. Leukemia 27, 534–540 (2013). https://doi.org/10.1038/leu.2012.268

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