Molecular mechanism of blastic crisis in chronic myelocytic leukemia.
Copyright policy )Molecular mechanism of blastic crisis in chronic myelocytic leukemia.
The t(3;21)(q26;q22), which is usually found in blastic crisis of chronic myelocytic leukemia or myelodysplastic syndrome-derived leukemia, produces an AML1/EVI-1 fusion protein of 180 kD containing amino-terminal half of AML1 including a runt homology domain which is fused to the entire of zinc finger EVI-1 protein. Thus, AML1/EVI-1 fusion protein is a chimeric transcription factor including a runt homology domain from AML1 and two zinc finger domains from EVI-1, totally three DNA binding domains, and an acidic domain from EVI-1. The AML1/EVI-1 fusion protein possesses the dual functions, namely, differentiation block and stimulation of proliferation. The ability of differentiation block depends on the runt homology domain in the AML1 part and the effect to stimulate proliferation depends on the second zinc finger domain in the EVI-1 portion. The AML1/EVI-1 could play an important role in leukemic progression of chronic myelocytic leukemia by these dual functions as a transcription factor.
- University of Tokyo Japan
Chromosomes, Human, Pair 21, Recombinant Fusion Proteins, Cell Differentiation, Transfection, MDS1 and EVI1 Complex Locus Protein, Translocation, Genetic, Cell Line, Neoplasm Proteins, Rats, DNA-Binding Proteins, Leukemia, Myelogenous, Chronic, BCR-ABL Positive, Proto-Oncogene Proteins, Core Binding Factor Alpha 2 Subunit, Proto-Oncogenes, Animals, Humans, Chromosomes, Human, Pair 3, Blast Crisis, Cell Division, Transcription Factors
Chromosomes, Human, Pair 21, Recombinant Fusion Proteins, Cell Differentiation, Transfection, MDS1 and EVI1 Complex Locus Protein, Translocation, Genetic, Cell Line, Neoplasm Proteins, Rats, DNA-Binding Proteins, Leukemia, Myelogenous, Chronic, BCR-ABL Positive, Proto-Oncogene Proteins, Core Binding Factor Alpha 2 Subunit, Proto-Oncogenes, Animals, Humans, Chromosomes, Human, Pair 3, Blast Crisis, Cell Division, Transcription Factors
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