Retroviral insertions in the CB-1/Fim-3 common site of integration activate expression of the Evi-1 gene.

A common retroviral integration site (CB-1) was identified in two IL-3-dependent myeloid leukemia cell lines (DA-3, DA-34). The CB-1 locus was mapped to murine chromosome 3 and was shown to be closely linked to another myeloid common site of viral integrations in myeloid leukemias, Evi-1. A comparison of the CB-1 restriction map with published restriction maps for other common integration sites demonstrated that it was nearly identical to the restriction map of a common site of Friend MuLV integration in myeloid tumors termed Fim-3 (Bordereaux et al. 1987). Genomic clones representing approximately 110 kb of the CB-1 locus and 80 kb of the 5' region of the Evi-1 locus demonstrate no physical overlap of these viral integration sites. Previous studies (Morishita et al. 1988) have shown that retroviral insertions in the Evi-1 locus activate the expression of a gene potentially encoding a 120 kd zinc finger protein. Evi-1 expression is also activated in cell lines with viral integrations in the CB-1 locus. These results demonstrate that the CB-1/Fim-3 and Evi-1 loci constitute a large genomic region in which viral integrations activate the transcription of a new potential myeloid transforming gene.