Novel MEIS1::NCOA2 fusion gene identified in 42-year-old woman with acute myeloid leukemia

Acute myeloid leukemia (AML) is a heterogeneous hematologic malignancy characterized by diverse genetic abnormalities, many of which serve as diagnostic, prognostic, and therapeutic markers. While various recurrent gene fusions are well-established drivers of AML, the MEIS1::NCOA2 fusion gene has primarily been associated with genitourinary and gynecologic sarcomas. Understanding the full spectrum of genetic alterations in AML is crucial for personalized treatment strategies, as novel fusions can reveal unique disease mechanisms and potential therapeutic vulnerabilities. This case highlights a previously uncharacterized genetic subtype within AML.

Researchers report the first case of acute myeloid leukemia (AML) in a 42-year-old woman presenting with a novel MEIS1::NCOA2 fusion. The fusion was initially identified through targeted RNA sequencing of the patient's samples. Subsequent validation was performed using Sanger sequencing to confirm the presence and precise breakpoints of the fusion gene. Genetic analysis further characterized the underlying chromosomal rearrangement as a t(2;8)(p14;q13.3) translocation, which is responsible for generating this specific fusion.

The study identified a novel MEIS1::NCOA2 fusion in a 42-year-old woman diagnosed with acute myeloid leukemia (AML), marking the first reported instance of this specific fusion in AML. This fusion arises from a t(2;8)(p14;q13.3) translocation. Crucially, the breakpoint within MEIS1 was found at exon 11, which differs significantly from the classic MEIS1 exons 6 or 7 breakpoints typically observed in sarcomas. The identified fusion retains nearly the full-length functional domains of MEIS1, which are known to be critical for leukemogenesis. This unique breakpoint suggests a potentially distinct mechanism contributing to AML pathogenesis, expanding the known genomic landscape of the disease. The presence of this fusion was rigorously validated by Sanger sequencing following initial detection via targeted RNA sequencing.