Generation of the AML1-EVI-1 fusion gene in the t(3;21)(q26;q22) causes blastic crisis in chronic myelocytic leukemia.
The t(3;21)(q26;q22) translocation, which is one of the consistent chromosomal abnormalities found in blastic crisis of chronic myelocytic leukemia (CML), is thought to play an important role in the leukemic progression of CML to an acute blastic crisis phase. The AML1 gene, which is located at the translocation breakpoint of the t(8;21)(q22;q22) translocation found in acute myelocytic leukemia, was also rearranged by the t(3;21)(q26;q22) translocation. Screening of a cDNA library of the t(3;21)-carrying leukemic cell line cells (SKH1) resulted in the isolation of two potentially complete AML1-EVI-1 chimeric cDNAs of 6 kb. Two species of AML1-EVI-1 fusion transcripts of 8.2 and 7.0 kb were detected in SKH1 cells. These cells expressed the 180 kDa AML1-EVI-1 fusion protein containing an N-terminal half of AML1 including a runt homology domain which is fused to the entire zinc finger EVI-1 protein. The AML1-EVI-1 fusion transcript was consistent in all three cases of the t(3;21)-carrying leukemia examined by RNA-based PCR. These findings strongly suggest that the t(3;21) translocation results in the formation of a new class of chimeric transcription factor which could contribute to the leukemic progression of CML through interference with cell growth and differentiation.
Mitani
K
K
Third Department of Internal Medicine, Faculty of Medicine, University of Tokyo, Japan.
Ogawa
S
S
Tanaka
T
T
Miyoshi
H
H
Kurokawa
M
M
Mano
H
H
Yazaki
Y
Y
Ohki
M
M
Hirai
H
H
D016475:3T3 Cells; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D001752:Blast Crisis / Q000235:genetics*; D015153:Blotting, Western; D002891:Chromosomes, Human, Pair 21; D002893:Chromosomes, Human, Pair 3; D003001:Cloning, Molecular; D050676:Core Binding Factor Alpha 2 Subunit; D004273:DNA, Neoplasm; D004268:DNA-Binding Proteins / Q000235:genetics; D006801:Humans; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000235:genetics* / Q000473:pathology; D000074008:MDS1 and EVI1 Complex Locus Protein; D051379:Mice; D008969:Molecular Sequence Data; D009363:Neoplasm Proteins / Q000235:genetics*; D011518:Proto-Oncogene Proteins; D011519:Proto-Oncogenes; D014157:Transcription Factors; D014178:Translocation, Genetic; D014407:Tumor Cells, Cultured
D050676:Core Binding Factor Alpha 2 Subunit; D004273:DNA, Neoplasm; D004268:DNA-Binding Proteins; D000074008:MDS1 and EVI1 Complex Locus Protein; C063575:MECOM protein, human; C499305:Mecom protein, mouse; D009363:Neoplasm Proteins; D011518:Proto-Oncogene Proteins; C493728:RUNX1 protein, human; C493726:Runx1 protein, mouse; D014157:Transcription Factors