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Activation of a Novel Gene in 3q21 and Identification of Intergenic Fusion Transcripts with Ecotropic Viral Insertion Site I in Leukemia¹

Eleanor Roosevelt Institute, Denver, Colorado 80206 [Y. P., A. R., K. G.]; Institute of Molecular Biology and Genetics, National Academy of Sciences of Ukraine, Kiev, 143, 25243 Ukraine [A. R.]; and Institut für Medizinische Biologie der Universität Wien, 1090 Vienna, Austria [R. W., C. F.]

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. GR6 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 transcripts between the ecotropic viral insertion site I (EVI1) gene in 3q26 and GR6 and between EVI1 and Ribophorin 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 EVI1 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-EVI1 fusions and ETV6-EVI1 fusions, respectively, occur. The Ribophorin I-EVI1 fusion in particular may be a common occurrence in t(3;3).

¹ This work was supported by The Dale Tooley Cancer Research Support Fund and American Cancer Society Grant VM-122 (to K. G.); National Cancer Institute Grant CA46934 to the University of Colorado Health Sciences Center Cancer Center (to K. G.); and FWF Grant P11803-GEN (to C. F.).

² To whom requests for reprints should be addressed, at Eleanor Roosevelt Institute, 1899 Gaylord Street, Denver, CO 80206.

Received 6/10/97. Accepted 7/28/97.

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