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Review: genetic models of acute myeloid leukaemia

Oncogene volume 27, pages 3765–3779 (2008)Cite this article

Abstract

The use of genetically engineered mice (GEM) have been critical in understanding disease states such as cancer, and none more so than acute myelogenous leukaemia (AML), a disease characterized by over 100 distinct chromosomal translocations. A substantial proportion of cases exhibiting recurrent reciprocal translocations at diagnosis, such as t(8;21) or t(15;17) have been exhaustively studied and are currently employed in clinical diagnosis. However, a definitive conclusion regarding the leukaemogenic potential of defined transgenes for this disease remains elusive. While it is increasingly apparent that a number of cooperating mutations are necessary to develop a leukaemic phenotype, the number of models reflecting these synergisms remains few. Furthermore, little emphasis has been paid to the effect of chromosomal translocations other than recurrent genetic abnormalities, with no models reflecting the multiple abnormalities observed in high-risk cases of AML accounting for 8–10% of adult AML. Here we review the differing technologies employed in generation of GEM of AML. We discuss the relevance of GEM AML from embryonic stem cell-mediated (for example retinoic acid receptor-α fusions and AML1/ETO) models; through to the valuable retroviral-mediated gene transfer models. The latter have been used to great effect in defining the transforming properties of chromosomal translocation products such as MLL (found in 5–6% of all AML cases) and NUP98 (denoting poor prognosis in therapy-related disease) and particularly when co-transduced with bad prognostic factors such as Flt3 mutations. Finally, we comment on the emergence of newer transduction technologies, which can regulate the level of expression to defined cell lineages in both primary murine and human xenografts, and discuss how combining multiple genetic modalities, more relevant models of this complex disease are being generated.

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Acknowledgements

This study was supported by Helse Vest Project numbers 911182 and 911388.

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Authors and Affiliations

  1. Institute of Medicine, Haematology Section, University of Bergen, Bergen, Norway

    E McCormack, O Bruserud & B T Gjertsen

  2. Department of Internal Medicine, Haematology Section, Haukeland University Hospital, Bergen, Norway

    E McCormack, O Bruserud & B T Gjertsen

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  1. E McCormack
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  2. O Bruserud
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Correspondence to B T Gjertsen.

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Supplementary Information accompanies the paper on the Oncogene website (http://www.nature.com/onc)

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McCormack, E., Bruserud, O. & Gjertsen, B. Review: genetic models of acute myeloid leukaemia. Oncogene 27, 3765–3779 (2008). https://doi.org/10.1038/onc.2008.16

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