The avian and mammalian ets genes: molecular characterization, chromosome mapping, and implication in human leukemia

The mammalian homologs of the ets-region from the transforming gene of avian erythroblastosis virus, E26, consist of two distinct domains located on different chromosomes. Using somatic cell hybrid panels, the mammalian homologs of the 5' v-ets-domain, ets-1, were mapped to chromosome 11 in man, to chromosome 9 in mouse, and to chromosome D1 in cat. The mammalian homologs of the 3'v-ets domain, ets-2, were similarly mapped to human chromosome 21, to mouse chromosome 16, and to feline chromosome C2. We conclude that the ets sequence shared by the virus, chicken, and man is likely to contain at least two functionally dissociable domains, identifiable as ets-1 and ets-2. The human ets- locus is transcriptionally active and encodes a single mRNA of 6.8 kb, while the second locus, human ets-2 encodes three mRNAs of 4.7, 3.2 and 2.7 kb. By contrast, the chicken homolog, having a contiguous ets-1 and ets-2 sequence, is primarily expressed in normal chicken cells as a single 7.5 kb mRNA. Because chromosome translocations have been associated with different human hematopoietic malignancies, we have used our human probes to study specific translocations occurring in acute leukemias. The human ets- gene was found to translocate from chromosome 11 to 4 in t(4;11) (q21;23) and the human ets-2 gene was found to translocate from chromosome 21 to 8 in t(8;21) (q22;q22). Significantly, both translocations were associated with an expression of ets genes which differed from that found in normal diploid lymphoid cells