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Modelling haematopoietic malignancies in the mouse and therapeutical implications

Abstract

Modelling human disease in the mouse has become an essential activity in biomedical research in order to unravel molecular mechanisms underlying pathological conditions as well as to determine in vivo the consequences of aberrant gene function. The mouse is by far the most accessible mammalian system physiologically similar to humans. Furthermore, the development of novel techniques for manipulating the murine genome, which allow the in vivo modification of virtually any genomic region in a time and/or tissue specific manner, renders the mouse an ideal model system to study human pathological conditions. Modelling human diseases in mice has reached an even greater relevance in the field of haematological malignancies, due to the already advanced characterization of the molecular basis of many haematological disorders. In this review, we describe the most important technological developments that made it possible to reproduce in the mouse the genetic lesions that characterize human haematological malignancies, thus often generating faithful mouse models of the human condition. We provide specific examples of the advantages and limitations of the various genetic approaches utilized to model leukaemia and lymphoma in the mouse. Finally, we discuss the power of mouse modelling in developing and testing novel therapeutic modalities in pre-clinical studies.

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Acknowledgements

This work is supported by the NCI, the De Witt Wallace Fund for Memorial Sloan-Kettering Cancer Center, the Mouse Model of Human Cancer Consortium (MMHCC) and NIH Grants to PP Pandolfi and the Lymphoma & Leukemia Society of which PP Pandolfi is a Scholar. Finally, we are indebted with all the past and present members of the laboratory of Molecular and Developmental Biology (MADB) lab at Memorial Sloan-Kettering Cancer Center, working on mouse modelling of cancer and related subjects.

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Correspondence to Pier Paolo Pandolfi.

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Bernardi, R., Grisendi, S. & Pandolfi, P. Modelling haematopoietic malignancies in the mouse and therapeutical implications. Oncogene 21, 3445–3458 (2002). https://doi.org/10.1038/sj.onc.1205313

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