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E2A-Pbx1, the t(1;19) translocation protein of human pre-B-cell acute lymphocytic leukemia, causes acute myeloid leukemia in mice

Kamps, Mark P. and Baltimore, David (1993) E2A-Pbx1, the t(1;19) translocation protein of human pre-B-cell acute lymphocytic leukemia, causes acute myeloid leukemia in mice. Molecular and Cellular Biology, 13 (1). pp. 351-357. ISSN 0270-7306. http://resolver.caltech.edu/CaltechAUTHORS:KAMmcb93

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Abstract

One-quarter of pediatric pre-B-cell leukemias contain the t(1;19) chromosomal translocation, which fuses 5' exons encoding the transactivation domain of the E2A transcription factor gene to 3' exons ecoding the putative DNA-binding region of the unusual homeobox gene, PBX1. To test the leukemic potential of this fused gene, a cDNA encoding its major protein product, p85E2A-Pbx1, was incorporated into a retrovirus construct and introduced into normal mouse marrow progenitors by infection. The cells were used in a bone marrow transplantation protocol to reconstitute the hematopoietic compartments of lethally irradiated recipients. After 3 to 8 months, reconstituted mice developed acute myeloid leukemias that expressed high levels of p85E2A-Pbx1 and were readily transmissible to immunocompetent mice. Most acute myeloid leukemias also grew as granulocytic sarcomas and exhibited some neutrophilic differentiation. These results demonstrate a causative role for p85E2A-Pbx1 in human acute leukemia and indicate that the oncogenic potential of Pbx1 is not limited to pre-B-cell malignancies.


Item Type:Article
Additional Information:Copyright © 1993 by the American Society for Microbiology. Received 24 June 1992/Returned for modification 20 July 1992/Accepted 29 September 1992 We are indebted to George Daley, Rick Van Etten, and Marty Scott for educational assistance in mouse and human hematology and oncology. M.P.K. was supported by Damon Runyon-Walter Winchell Cancer Research Fund fellowship DRG-982. This work was also supported by Public Health Service grant GM 39458 and National Institutes of Health grant CA56876-01.
Record Number:CaltechAUTHORS:KAMmcb93
Persistent URL:http://resolver.caltech.edu/CaltechAUTHORS:KAMmcb93
Alternative URL:http://mcb.asm.org/cgi/content/abstract/13/1/351
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ID Code:8732
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Deposited On:11 Sep 2007
Last Modified:26 Dec 2012 09:41

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