Retroviral transduction model of mixed lineage leukemia fused to CREB binding protein.
The in-frame fusion of mixed lineage leukemia to CREB binding protein has been cloned from several patients with t-acute myeloid leukemia and a t(11;16)(q23;p13). A murine retroviral transduction model of mixed lineage leukemia fused to CREB binding protein successfully recapitulates the disease. Interestingly, the mice also develop a preleukemic phase reminiscent of what is often seen in patients with t(11;16). From this work, it was determined that minimally, the amino terminus of mixed lineage leukemia fused to the bromodomain and histone acetyltransferase domain of CREB binding protein are necessary for developing acute myeloid leukemia. This model provides a useful tool for understanding the biologic basis of mixed lineage leukemia leukemogenesis and for developing and testing potential therapeutic agents.
Liedman
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Loyola University Medical Center, 2160 S. First Avenue, Maywood, IL 60153, USA.
Zeleznik-Le
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D000818:Animals; D019677:Artificial Gene Fusion; D050882:CREB-Binding Protein; D004268:DNA-Binding Proteins / Q000235:genetics*; D004195:Disease Models, Animal; D011495:Histone-Lysine N-Methyltransferase; D007951:Leukemia, Myeloid / Q000209:etiology*; D051379:Mice; D051788:Myeloid-Lymphoid Leukemia Protein; D009196:Myeloproliferative Disorders / Q000209:etiology; D009687:Nuclear Proteins / Q000235:genetics*; D011519:Proto-Oncogenes; D012190:Retroviridae / Q000235:genetics*; D015534:Trans-Activators / Q000235:genetics*; D014157:Transcription Factors; D014161:Transduction, Genetic
D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D015534:Trans-Activators; D014157:Transcription Factors; D051788:Myeloid-Lymphoid Leukemia Protein; D011495:Histone-Lysine N-Methyltransferase; C497423:Kmt2a protein, mouse; D050882:CREB-Binding Protein; C494364:Crebbp protein, mouse