Activation of a Novel Gene in 3q21 and Identification of Intergemc Fusion Transcripts with Ecotropic Viral Insertion Site I in Leukemia'

We have identified a novel gene, GR6, located Within the leukemia breakpoint region of 3q21, that is normally expressed in early fetal development but not in adult peripheral blood. CR6 is activated in the UCSD-AML1 cell line and in a leukemic sample, both of which carry a t(3;3)(q21;q26). In UCSD-AML1, we have also identified fusion tran scripts between the ecotropic viral insertion site I (EVIl) gene In 3q26 and GR6 and between EVIl and Rlbophorin I that maps 30 kb telomeric to GR6 in 3q21. All fusions splice the 5' ends of the 3q21 genes Into exon 2 of the EVil gene, an event that is similar to the normal intergenic splicing of MDS1-EVI1 and to those previously documented in leukemias with t(3;21) and t(3;12), in which acute myelogenous leukemia 1-EVIl fusions and ETV6-EVI1 fusions, respectively, occur. The Ribophorin I-EVIl fusion in particular may be a common occurrence in t(3;3).