1. ¹Department of Genetics and Tumor Cell Biology, St Jude Children's Research Hospital, Memphis, TN, USA
2. ²Department of Pathology, St Jude Children's Research Hospital, Memphis, TN, USA
3. ³Department of Pathology, Josephine Nefkens Institute, Erasmus MC, Rotterdam, The Netherlands
4. ⁴Oncogenesis and Development Section, National Human Genome Research Institute, NIH, Bethesda, MD, USA

Correspondence: Dr GC Grosveld, Department of Genetics and Tumor Cell Biology, St Jude Children's Research Hospital, 332 North Lauderdale, Memphis, TN 38105-0318, USA. E-mail: gerard.grosveld@stjude.org

Received 27 April 2007; Accepted 30 April 2007; Published online 24 May 2007.

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 Cbf–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.