Activation of EVI1 transcripts with chromosomal translocation joining the TCRV beta 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-MO) had unique phenotypes of undifferentiated leukemia cells with expression of bo th 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. T herefore, we further characterized the chromosomal breakpoint by pulsed-fie ld gel electrophoresis near EVI1. We identified and isolated the chromosoma l breakpoint at approximately 80 kb upstream from the 5' end of EVI1. Seque nce analysis of the breakpoint revealed that the whole VP region from T cel l receptor beta (TCR beta) at 7q35 was translocated to the upstream of EVI1 . A 1.0 kb TCR beta transcript was expressed in the Kasumi-3 cells, suggest ing that TCR beta rearrangement occurred as D beta-J beta joining events. F luorescence in situ hybridization analysis revealed that the inverted chrom osome 7q22-q35 segment between TCR beta and the region proximal to the eryt hropoietin gene at 7q22 was translocated to the region distal to EVI1 in de r(3). Since the telomeric region of chromosome 8 q was also translocated to the inverted chromosome 7q22-q35 segment in der(3), the chromosomal abnorm alities of der(3) were defined as being der(3)t(3;7;8)(3pter-3q26: :7q35-7q 22::8q22-8qter). It is suggested that a translocated enhancer element in th e TCR beta locus and/or loss of a negative regulatory element near EVI1 mig ht function to enhance the EVI1 expression. Therefore, the enhanced EVI1 ex pression may contribute to the development of a subset of undifferentiated leukemia.