E2A-Pbx1, the t(1;19) translocation protein of human pre-B-cell acute lymphocytic leukemia, causes acute myeloid leukemia in mice.
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.
Kamps
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MP
Whitehead Institute for Biomedical Research, Cambridge, Massachusetts 02142.
Baltimore
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D000818:Animals; D002454:Cell Differentiation; D002878:Chromosomes, Human, Pair 1; D002888:Chromosomes, Human, Pair 19; D002999:Clone Cells; D004268:DNA-Binding Proteins / Q000235:genetics*; D005260:Female; D005801:Genes, Homeobox; D006133:Growth Substances / Q000494:pharmacology; D006410:Hematopoiesis; D018398:Homeodomain Proteins / Q000235:genetics*; D006801:Humans; D007951:Leukemia, Myeloid / Q000235:genetics / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D015514:Oncogene Proteins, Fusion / Q000235:genetics*; D009857:Oncogenes; D015452:Precursor B-Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics*; D051820:TCF Transcription Factors; D058125:Transcription Factor 7-Like 1 Protein; D014157:Transcription Factors / Q000235:genetics*; D014178:Translocation, Genetic
D004268:DNA-Binding Proteins; D006133:Growth Substances; D018398:Homeodomain Proteins; D015514:Oncogene Proteins, Fusion; D051820:TCF Transcription Factors; C544912:TCF7L1 protein, human; C544913:Tcf7l1 protein, mouse; D058125:Transcription Factor 7-Like 1 Protein; D014157:Transcription Factors; C089847:E2A-Pbx1 fusion protein