Molecular Characterization of NRG Gene, a Novel Partner, Fused to NUP98 Gene as a Result of the t(3;11)(q29q13;p15) Translocation in an Acute Myeloid/T Lymphocytic Leukemia.

The NUP98 gene has been reported to be fused with at least 17 partner genes in leukemia with 11p15 translocation. An adult patient with de novo acute myeloid/T lymphocytic leukemia harboring t(3;11)(q29q13;p15) has been investigated to characterize the genes involved in that translocation. Through molecular cytogenetic analysis, we identified a fusion transcript between NUP98 gene and a novel partner gene named as NUP98 related gene (NRG) at 3q29. Further molecular analysis showed that exon 13 of NUP98 was fused in-frame to exon 10 of NRG. Moreover, the segment from 3q13 to 3q29 translocated at 11p15 had been inverted and accompanied by the deletion of the distal portion of breakpoint at chromosome 3q29. Interestingly, the NUP98-NRG protein showed nuclear and cytoplasmic distribution, a pattern different from that of wild type NUP98 or NRG. When assayed in a GAL 4 reporter system, the fusion gene showed an aberrant trans-regulatory activity. Transfection in HL-60 cells demonstrated that NUP98-NRG could promote cell proliferation, survival and arrest differentiation. Therefore, NUP98-NRG may exert transforming effects by interfering with the cellular mechanism of transcriptional regulation. Our data provide thus new evidence that NUP98-related molecular abnormality is a recurrent genetic event in leukemogenesis.