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Blood. 2014 Dec 4;124(24):3608-12. doi: 10.1182/blood-2014-04-564666. Epub 2014 Oct 22.

Modeling de novo leukemogenesis from human cord blood with MN1 and NUP98HOXD13.

Author information

  • 1Terry Fox Laboratory, British Columbia Cancer Agency, Vancouver, British Columbia, Canada;
  • 2Department of Hematology, Hemostasis, Oncology, and Stem Cell Transplantation, Hannover Medical School, Hannover, Germany;
  • 3Division of Hematology, Hematologic Malignancies, University of Colorado AMC, Aurora, CO;
  • 4Department of Medicine, Hematology and Oncology, University of Frankfurt, Frankfurt/Main, Germany;
  • 5Department of Pathology, Seoul St. Mary's Hospital, The Catholic University of Korea, Seoul, Korea;
  • 6Department of Laboratory Medicine, Medical School of Inha University, Incheon, Korea; and.
  • 7Terry Fox Laboratory, British Columbia Cancer Agency, Vancouver, British Columbia, Canada; Department of Medicine, University of British Columbia, Vancouver, British Columbia, Canada.


Leukemic transformation of human cells is a complex process. Here we show that forced expression of MN1 in primitive human cord blood cells maintained on stromal cells in vitro induces a transient, but not serially transplantable, myeloproliferation in engrafted mice. However, cotransduction of an activated HOX gene (NUP98HOXD13) with MN1 induces a serially transplantable acute myeloid leukemia (AML). Further characterization of the leukemic cells generated from the dually transduced cells showed the activation of stem cell gene expression signatures also found in primary human AML. These findings show a new forward genetic model of human leukemogenesis and further highlight the relevance of homeobox transcription factors in the transformation process.

© 2014 by The American Society of Hematology.

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