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NPMc+ and FLT3_ITD mutations cooperate in inducing acute leukaemia in a novel mouse model

Leukemia volume 27, pages 2248–2251 (2013)Cite this article

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Acute myelogenous leukaemia (AML) is the most common type of leukaemia in adults and is responsible for more than 40% of leukaemia-related deaths. Karyotypic abnormalities have been widely used as a prognostic factor for risk stratification, leading to the identification of three risk-based groups: favourable, intermediate and unfavourable.1 The intermediate group includes cytogenetically normal AMLs (CN-AML; about 50% of all cases) and it is quite heterogeneous in terms of prognosis. Indeed, in these patients, the mutation status of different genes, in particular FLT3 (Fms-related Tyrosine Kinase 3) and NPM (Nucleophosmin), has important prognostic implications on the treatment outcome.2, 3 Patients with mutated NPM (NPMc+) have a favourable outcome,4 while patients with mutations in the FLT3 gene (FLT3-ITD) generally have a poor prognosis.5 Interestingly, these two mutations are frequently associated in CN-AML patients, strongly suggesting that they cooperate to some extent in leukaemia development.3 Patients with both mutations have a poor prognosis with respect to those only bearing the NPMc+ mutation and a better prognosis compared to those with the FLT3-ITD mutation alone.6 These observations indicate complex interactions among different mutations, pointing out their important prognostic value. Model systems of AMLs with either one or both mutations are needed to investigate their relative contribution to leukaemogenesis.

Here we report the results of our study on a new mouse model of NPMc+-dependent leukaemia, showing the effect of the combination of NPMc+ and FLT3-ITD mutations on leukaemia development in this model.

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Acknowledgements

MM has a fellowship from Fondazione Umberto Veronesi (FUV). This work was supported by grants from Associazione Italiana Ricerca sul Cancro (AIRC) and Ministero della Salute to EC and PGP. We thank Roberta Aina for editing the manuscript.

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Authors and Affiliations

  1. Department of Experimental Oncology, European Institute of Oncology, Milan, Italy

    M Mallardo, A Caronno, P G Pelicci & E Colombo

  2. Division of Pathology, European Institute of Oncology, Milan, Italy

    G Pruneri & P R Raviele

  3. Department of Medicine, Surgery and Dentistry, University of Milan, Milan, Italy

    G Pruneri, P G Pelicci & E Colombo

  4. Department of Genomic Medicine, MD Anderson Cancer Center, Houston, TX, USA

    A Viale

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  1. M Mallardo
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  2. A Caronno
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  3. G Pruneri
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  4. P R Raviele
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  5. A Viale
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  6. P G Pelicci
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  7. E Colombo
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Corresponding authors

Correspondence to P G Pelicci or E Colombo.

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The authors declare no conflict of interest.

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Research on animals

The corresponding authors declare that the described study conforms to all the regulations protecting animals used for research purpose. The procedures related to animal use have been communicated and have been approved by the Italian Ministry of Health.

Author contributions

MM and AC performed most of the experiments. GP and PRR performed immunohistochemistry experiments on mouse specimens. AV contributed to study design and supervised the experimental work. PGP and EC designed the study, supervised the experimental work, and wrote and critically revised the manuscript.

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Mallardo, M., Caronno, A., Pruneri, G. et al. NPMc+ and FLT3_ITD mutations cooperate in inducing acute leukaemia in a novel mouse model. Leukemia 27, 2248–2251 (2013). https://doi.org/10.1038/leu.2013.114

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