Human AML1/MDS1/EVI1 fusion protein induces an acute myelogenous leukemia (AML) in mice: a model for human AML.
The human t(3;21)(q26;q22) translocation is found as a secondary mutation in some cases of chronic myelogenous leukemia during the blast phase and in therapy-related myelodysplasia and acute myelogenous leukemia. One result of this translocation is a fusion between the AML1, MDS1, and EVI1 genes, which encodes a transcription factor of approximately 200 kDa. The role of the AML1/MDS1/EVI1 (AME) fusion gene in leukemogenesis is largely unknown. In this study, we analyzed the effect of the AME fusion gene in vivo by expressing it in mouse bone marrow cells via retroviral transduction. We found that mice transplanted with AME-transduced bone marrow cells suffered from an acute myelogenous leukemia (AML) 5-13 mo after transplantation. The disease could be readily transferred into secondary recipients with a much shorter latency. Morphological analysis of peripheral blood and bone marrow smears demonstrated the presence of myeloid blast cells and differentiated but immature cells of both myelocytic and monocytic lineages. Cytochemical and flow cytometric analysis confirmed that these mice had a disease similar to the human acute myelomonocytic leukemia. This murine model for AME-induced AML will help dissect the molecular mechanism of AML and the molecular biology of the AML1, MDS1, and EVI1 genes.
Cuenco
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GM
Rosenstiel Basic Medical Sciences Research Center, Department of Biology, Brandeis University, Waltham, MA 02454, USA.
Nucifora
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Ren
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D000818:Animals; D001854:Bone Marrow Cells; D002460:Cell Line; D050676:Core Binding Factor Alpha 2 Subunit; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics; D006651:Histocytochemistry; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000235:genetics*; D000074008:MDS1 and EVI1 Complex Locus Protein; D051379:Mice; D009363:Neoplasm Proteins; D009374:Neoplasms, Experimental; D011506:Proteins / Q000235:genetics* / Q000378:metabolism; D011518:Proto-Oncogene Proteins; D011519:Proto-Oncogenes; D011993:Recombinant Fusion Proteins / Q000235:genetics* / Q000378:metabolism; D012190:Retroviridae / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism; D014161:Transduction, Genetic; D014162:Transfection; D014178:Translocation, Genetic / Q000235:genetics
D050676:Core Binding Factor Alpha 2 Subunit; D004268:DNA-Binding Proteins; D000074008:MDS1 and EVI1 Complex Locus Protein; C063575:MECOM protein, human; C499305:Mecom protein, mouse; D009363:Neoplasm Proteins; D011506:Proteins; D011518:Proto-Oncogene Proteins; C493728:RUNX1 protein, human; D011993:Recombinant Fusion Proteins; C493726:Runx1 protein, mouse; D014157:Transcription Factors