Identification of the UBA2-WTIP fusion gene in acute myeloid leukemia

Abstract

Identifying and targeting oncogenic fusion genes have revolutionized the treatment of leukemia, such as PML-RARα fusion gene in acute promyelocytic leukemia. Here we identified an intrachromosomal fusion gene located on chromosome 19q.13 between UBA2 and WTIP gene in a case of acute myeloid leukemia. The UBA2-WTIP fusion gene contains the N-terminal E1_enzyme_family, VAE_Ubl domains of UBA2, and the C-terminal LIM domains of WTIP. The UBA2-WTIP fusion was detected by reverse transcriptase polymerase chain reaction and Sanger sequencing in 19 of 56 acute myeloid leukemia samples (33.9%). Ectopic expression of the UBA2-WTIP fusion in human acute myeloid leukemia KG-1a cells showed enhanced cell proliferation both in vitro and in vivo. The UBA2-WTIP fusion induced phosphorylation of STAT3, STAT5 and ERK1/2, and abrogates WTIP-mediated mammalian processing body formation. Finally, triptolide displayed selective cytotoxicity against KG-1a cells harboring the UBA2-WTIP fusion. Collectively, our findings suggest that the UBA2-WTIP fusion is an oncogenic fusion gene, as well as a promising therapeutic target for the treatment of acute myeloid leukemia.

Keywords: Acute myeloid leukemia; Fusion gene; UBA2; WTIP.