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Acute Leukemias

MN1 overexpression is an important step in the development of inv(16) AML

Leukemia volume 21, pages 1679–1690 (2007)Cite this article

Abstract

The gene encoding the transcriptional co-activator MN1 is the target of the reciprocal chromosome translocation (12;22)(p13;q12) in some patients with acute myeloid leukemia (AML). In addition, expression array analysis showed that MN1 was overexpressed in AML specified by inv(16), in some AML overexpressing ecotropic viral integration 1 site (EVI1) and in some AML without karyotypic abnormalities. Here we describe that mice receiving transplants of bone marrow (BM) overexpressing MN1 rapidly developed myeloproliferative disease (MPD). This BM also generated myeloid cell lines in culture. By mimicking the situation in human inv(16) AML, forced coexpression of MN1 and Cbfβ–SMMHC rapidly caused AML in mice. These findings identify MN1 as a highly effective hematopoietic oncogene and suggest that MN1 overexpression is an important cooperative event in human inv(16) AML.

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Acknowledgements

We thank Dr Jerold Rehg for the pathological analysis of the mice, Dr Richard Ashmun and Ann-Mary Hamilton Easton for expert FACS analysis and Blake McGourty for the supply of C57Bl/6/129svJ mixed-background mice. This work was supported by NCI Grant CA72999, the Cancer Center (CORE) support grant CA021765, the Dutch Cancer Society Grants EUR98-1778 and DDHK2003-2869, the Intramural Research Programs of NHGRI, NIH and by the American Lebanese Syrian Associated Charities (ALSAC).

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Authors and Affiliations

  1. Department of Genetics and Tumor Cell Biology, St Jude Children's Research Hospital, Memphis, TN, USA

    C Carella, J Bonten, S Sirma, T A Kranenburg, S Terranova, R Klein-Geltink & G C Grosveld

  2. Department of Pathology, St Jude Children's Research Hospital, Memphis, TN, USA

    S Shurtleff & J R Downing

  3. Department of Pathology, Josephine Nefkens Institute, Erasmus MC, Rotterdam, The Netherlands

    E C Zwarthoff

  4. Oncogenesis and Development Section, National Human Genome Research Institute, NIH, Bethesda, MD, USA

    P P Liu

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  1. C Carella
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Correspondence to G C Grosveld.

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Supplementary information accompanies the paper on the Leukemia Web site (http://www.nature.com/leu)

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Carella, C., Bonten, J., Sirma, S. et al. MN1 overexpression is an important step in the development of inv(16) AML. Leukemia 21, 1679–1690 (2007). https://doi.org/10.1038/sj.leu.2404778

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