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Molecular and Cellular Biology, January 2001, p. 224-234, Vol. 21, No. 1
0270-7306/01/$04.00+0 DOI: 10.1128/MCB.21.1.224-234.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

Defining Roles for HOX and MEIS1 Genes in Induction of Acute Myeloid Leukemia

Unnur Thorsteinsdottir,1 Evert Kroon,1 Lori Jerome,1 Francesco Blasi,2 and Guy Sauvageau1,3,4,*

Laboratory of Molecular Genetics of Hemopoietic Stem Cells, Clinical Research Institute of Montréal, Montréal, Québec H2W 1R7,1 Department of Medicine, Université de Montréal, Montréal, Québec H3C 3J7,3 and Division of Hematology, Maisonneuve-Rosemont Hospital, Université de Montréal, Montréal, Québec H1T 2M2,4 Canada, and Molecular Genetics Unit, DIBIT, Universita Vita-Salute San Raffaele, 20132 Milan, Italy2

Received 21 July 2000/Returned for modification 13 September 2000/Accepted 12 October 2000

Complex genetic and biochemical interactions between HOX proteins and members of the TALE (i.e., PBX and MEIS) family have been identified in embryonic development, and some of these interactions also appear to be important for leukemic transformation. We have previously shown that HOXA9 collaborates with MEIS1 in the induction of acute myeloid leukemia (AML). In this report, we demonstrate that HOXB3, which is highly divergent from HOXA9, also genetically interacts with MEIS1, but not with PBX1, in generating AML. In addition, we show that the HOXA9 and HOXB3 genes play key roles in establishing all the main characteristics of the leukemias, while MEIS1 functions only to accelerate the onset of the leukemic transformation. Contrasting the reported functional similarities between PREP1 and MEIS1, such as PBX nuclear retention, we also show that PREP1 overexpression is incapable of accelerating the HOXA9-induced AML, suggesting that MEIS1 function in transformation must entail more than PBX nuclear localization. Collectively, these data demonstrate that MEIS1 is a common leukemic collaborator with two structurally and functionally divergent HOX genes and that, in this collaboration, the HOX gene defines the identity of the leukemia.

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

Molecular and Cellular Biology, January 2001, p. 224-234, Vol. 21, No. 1
0270-7306/01/$04.00+0 DOI: 10.1128/MCB.21.1.224-234.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.


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