WNT inhibitory factor 1 (WIF1) is a novel fusion partner of RUNX family transcription factor 1 (RUNX1) in acute myeloid leukemia with t(12;21)(q14;q22).

Abstract

As a member of the core transcription factor family, RUNX1 plays an important role in stem cell differentiation. RUNX1 rearrangements are common in myeloid and lymphoid tumors [1]. (Blood 129(15):2070-2082, 2017). One of the most commonly detected abnormalities in acute myeloid leukemia (AML) is the translocation t(8;21)(q22;q22) (Blood Adv 4(1):229-238, 2020), resulting in a RUNX1::RUNX1T1 fusion. Occasionally, RUNX1 is translocated with other genes. This article describes an AML patient with a specific chromosomal translocation involving the RUNX1 gene and the identification of the RUNX1::WIF1 fusion. Chromosomal abnormalities were detected through karyotype analysis, break gene involved was identified via fluorescence in situ hybridization (FISH), and the novel fusion was identified through transcriptome sequencing and subsequently confirmed through reverse transcription-polymerase chain reaction (RT-PCR) and Sanger sequencing. A 79-year-old female patient diagnosed with AML was found to have a t(12;21)(q14;q12) translocation. FISH analysis provided evidence of RUNX1 gene rearrangement. Additionally, transcriptomic sequencing revealed a novel fusion known as RUNX1::WIF1, which consists of RUNX1 exon 2 and WIF1 exon 3. The novel fusion was further confirmed through RT-PCR and Sanger sequencing. We identified WIF1 as a novel fusion partner of RUNX1 in AML. Additionally, this is the first report of a RUNX1 fusion gene with the break point in intron 2, resulting in an out-of-frame fusion. Further research is needed to investigate the impact of this novel fusion on the establishment and progression of the disease.