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.
Mitani
K
K
Third Department of Internal Medicine, Faculty of Medicine, University of Tokyo, Japan.
D000818:Animals; D001752:Blast Crisis / Q000235:genetics*; D002454:Cell Differentiation; D002455:Cell Division; D002460:Cell Line; D002891:Chromosomes, Human, Pair 21; D002893:Chromosomes, Human, Pair 3; D050676:Core Binding Factor Alpha 2 Subunit; D004268:DNA-Binding Proteins / Q000096:biosynthesis / Q000235:genetics; D006801:Humans; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000235:genetics* / Q000473:pathology*; D000074008:MDS1 and EVI1 Complex Locus Protein; D009363:Neoplasm Proteins / Q000096:biosynthesis; D011518:Proto-Oncogene Proteins; D011519:Proto-Oncogenes; D051381:Rats; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis / Q000235:genetics; D014157:Transcription Factors / Q000096:biosynthesis / Q000235:genetics; D014162:Transfection; D014178:Translocation, Genetic; D018909:src Homology Domains
D050676:Core Binding Factor Alpha 2 Subunit; D004268:DNA-Binding Proteins; D000074008:MDS1 and EVI1 Complex Locus Protein; C063575:MECOM protein, human; D009363:Neoplasm Proteins; D011518:Proto-Oncogene Proteins; C493728:RUNX1 protein, human; D011993:Recombinant Fusion Proteins; C493727:Runx1 protein, rat; D014157:Transcription Factors