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Molecular and Cellular Biology, September 1999, p. 6355-6366, Vol. 19, No. 9
0270-7306/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.

The Oncoprotein E2A-Pbx1a Collaborates with Hoxa9 To Acutely Transform Primary Bone Marrow Cells

Unnur Thorsteinsdottir,1 Jana Krosl,1 Evert Kroon,1 André Haman,1 Trang Hoang,1,2 and Guy Sauvageau1,3,4,*

Laboratory of Molecular Genetics of Hemopoietic Stem Cells, Clinical Research Institute of Montréal, Montréal, Québec, Canada H2W 1R7,1 and Departments of Pharmacology2 and Medicine3 and Division of Hematology Maisonneuve-Rosemont Hospital,4 Université de Montréal, Montréal, Québec, Canada H3C 3J7

Received 9 February 1999/Returned for modification 5 April 1999/Accepted 3 June 1999

A recurrent translocation between chromosome 1 (Pbx1) and 19 (E2A) leading to the expression of the E2A-Pbx1 fusion oncoprotein occurs in ~5 to 10% of acute leukemias in humans. It has been proposed that some of the oncogenic potential of E2A-Pbx1 could be mediated through heterocomplex formation with Hox proteins, which are also involved in human and mouse leukemias. To directly test this possibility, mouse bone marrow cells were engineered by retroviral gene transfer to overexpress E2A-Pbx1a together with Hoxa9. The results obtained demonstrated a strong synergistic interaction between E2A-Pbx1a and Hoxa9 in inducing growth factor-independent proliferation of transduced bone marrow cells in vitro and leukemic growth in vivo in only 39 ± 2 days. The leukemic blasts which coexpress E2A-Pbx1a and Hoxa9 showed little differentiation and produced cytokines such as interleukin-3, granulocyte colony-stimulating factor, and Steel. Together, these studies demonstrate that the Hoxa9 and E2A-Pbx1a gene products collaborate to produce a highly aggressive acute leukemic disease.

* Corresponding author. Mailing address: Institut de Recherches Cliniques de Montréal, 110 Pine Ave. West, Montréal, Québec, Canada H2W 1R7. Phone: 514-987-5797. Fax: 514-987-5718. E-mail: sauvagg{at}ircm.qc.ca.

Molecular and Cellular Biology, September 1999, p. 6355-6366, Vol. 19, No. 9
0270-7306/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.


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