Activation of EVI1 transcripts with chromosomal translocation joining the TCRVbeta locus and the EVI1 gene in human acute undifferentiated leukemia cell line (Kasumi-3) with a complex translocation of der(3)t(3;7;8).
A cell line (Kasumi-3) established from acute myeloid leukemia (AML-M0) had unique phenotypes of undifferentiated leukemia cells with expression of both T cell and myeloid antigens. Kasumi-3 cells with t(3;7)(q26;q22) highly expressed a 6 kb transcript of EVI1, which is located on chromosome 3q26. Therefore, we further characterized the chromosomal breakpoint by pulsed-field gel electrophoresis near EVI1. We identified and isolated the chromosomal breakpoint at approximately 80 kb upstream from the 5' end of EVI1. Sequence analysis of the breakpoint revealed that the whole Vbeta region from T cell receptor beta (TCRbeta) at 7q35 was translocated to the upstream of EVI1. A 1.0 kb TCRbeta transcript was expressed in the Kasumi-3 cells, suggesting that TCRbeta rearrangement occurred as Dbeta-Jbeta joining events. Fluorescence in situ hybridization analysis revealed that the inverted chromosome 7q22-q35 segment between TCRbeta and the region proximal to the erythropoietin gene at 7q22 was translocated to the region distal to EVI1 in der(3). Since the telomeric region of chromosome 8 q was also translocated to the inverted chromosome 7q22-q35 segment in der(3), the chromosomal abnormalities of der(3) were defined as being der(3)t(3;7;8)(3pter-3q26::7q35-7q22::8q22 -8qter). It is suggested that a translocated enhancer element in the TCRbeta locus and/or loss of a negative regulatory element near EVI1 might function to enhance the EVI1 expression. Therefore, the enhanced EVI1 expression may contribute to the development of a subset of undifferentiated leukemia.
Suzukawa
K
K
Biology Division, National Cancer Center Research Institute, Tokyo, Japan.
Kodera
T
T
Shimizu
S
S
Nagasawa
T
T
Asou
H
H
Kamada
N
N
Taniwaki
M
M
Yokota
J
J
Morishita
K
K
D000208:Acute Disease; D001483:Base Sequence; D002454:Cell Differentiation / Q000502:physiology; D002874:Chromosome Mapping; D002893:Chromosomes, Human, Pair 3; D002897:Chromosomes, Human, Pair 7; D019674:Genes, T-Cell Receptor beta; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007951:Leukemia, Myeloid / Q000235:genetics*; D008969:Molecular Sequence Data; D011519:Proto-Oncogenes; D012333:RNA, Messenger / Q000096:biosynthesis; D014178:Translocation, Genetic; D014407:Tumor Cells, Cultured
D012333:RNA, Messenger