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  • The EMBO Journal (2001) 20, 350 - 361
  • doi:10.1093/emboj/20.3.350

NUP98–HOXA9 expression in hemopoietic stem cells induces chronic and acute myeloid leukemias in mice

Evert Kroon1, Unnur Thorsteinsdottir1, Nadine Mayotte1, Takuro Nakamura2 and Guy Sauvageau1,3,4

  1. Laboratory of Molecular Genetics of Hemopoietic Stem Cells, Clinical Research Institute of Montréal, Montréal, Québec, H2W 1R7, Canada
  2. Department of Carcinogenesis, The Cancer Institute, Tokyo, Japan
  3. Département de Médecine, Université de Montréal, Montréal, Québec, H3J 3J7, Canada
  4. Département d'Hématologie, Hôpital Maisonneuve-Rosemont, Montréal, Québec, H1T 2M2 Canada

Correspondence to:

Guy Sauvageau, E-mail: sauvagg@ircm.qc.ca

Received 20 July 2000; Accepted 11 December 2000; Revised 11 December 2000

Here we describe hemopoietic chimeras serving as a mouse model for NUP98–HOXA9-induced leukemia, which reproduced several of the phenotypes observed in human disease. Mice transplanted with bone marrow cells expressing NUP98–HOXA9 through retroviral transduction acquire a myeloproliferative disease (MPD) and eventually succumb to acute myeloid leukemia (AML). The NUP98 portion of the fusion protein was shown to be responsible for transforming a clinically silent pre-leukemic phase observed for Hoxa9 into a chronic, stem cell-derived MPD. The co-expression of NUP98–HOXA9 and Meis1 accelerated the transformation of MPD to AML, identifying a genetic interaction previously observed for Hoxa9 and Meis1. Our findings demonstrate the presence of overlapping yet distinct molecular mechanisms for MPD versus AML, illustrating the complexity of leukemic transformation.

  • Keywords:

    • AML,
    • Hox,
    • Meis,
    • NUP98–HOXA9,
    • PBX