A Novel MEIS1::NCOA2 Fusion Gene in Acute Myeloid Leukemia.

Abstract

MEIS1::NCOA2 is a recurrent fusion gene primarily associated with genitourinary and gynecologic sarcomas, with no reported association with acute myeloid leukemia (AML) to date. We report the first case of AML in a 42-year-old woman with a novel MEIS1::NCOA2 fusion, identified by targeted RNA sequencing and validated by Sanger sequencing. This fusion arises from a t(2;8)(p14;q13.3) translocation that fuses MEIS1 exon 11 to NCOA2 exon 14; its MEIS1 breakpoint differs from the classic exons 6/7 in sarcomas and retains nearly the full-length functional domains of MEIS1 that are critical for leukemogenesis. This case expands the genomic and disease spectrum of MEIS1::NCOA2, identifies a unique AML-associated breakpoint with potential leukemogenic roles, and warrants further functional and therapeutic investigation of this fusion gene.