A novel RUNX1::ANKLE2 fusion in high-risk MDS with progression to AML: a case report

Background The unusual RUNX1 fusion partners in myelodysplastic syndromes (MDS) are not well-known. We present the laboratory features, diagnostic features and clinical course of a patient with MDS who progressed to acute myeloid leukemia (AML) and harbored a novel RUNX1::ANKLE2 fusion. Case presentation A 71-year-old man was diagnosed with myelodysplastic syndrome with increased blasts-2 (MDS-IB-2), presenting with pancytopenia, multilineage dysplasia, and 15% bone marrow blasts. Targeted DNA sequencing found some adverse-risk mutations, and targeted RNA sequencing discovered a new in-frame RUNX1::ANKLE2 fusion caused by a cryptic t(12;21)(q24.33;q22.12) translocation. The patient rapidly progressed to AML and achieved (measurable residual disease) MRD negativity following treatment with the (Venetoclax combined with azacytidine) VA regimen. Conclusion This is the first reported case of MDS with a RUNX1::ANKLE2 fusion. This case demonstrates the necessity of targeted RNA sequencing for detecting cryptic and previously unrecognized gene fusions that may be missed by conventional cytogenetic or DNA-based approaches. Although the clinical and biological significance of RUNX1::ANKLE2 remains uncertain, its identification expands the spectrum of RUNX1 fusion partners in myeloid neoplasms. Further cases and functional studies are needed to determine whether this fusion contributes to disease progression or represents a rare, incidental event.