Optical genome mapping identifies novel ENOX2::RUNX1 t(X;21)(q26.1;q22.12) rearrangement in acute myeloid leukemia-myelodysplasia related: first case report.

BACKGROUND

Acute myeloid leukemia-myelodysplasia related (AML-MR) is a biologically and clinically distinct subtype of AML that arises in the context of prior dysplasia. It is characterized by adverse cytogenetics and poor prognosis compared to other AML subtypes. Several genetic mechanisms underpin the pathogenesis of AML-MR; however, additional findings are likely to come to light over time with advanced genomic technologies, enhancing our understanding of their evolution. This report details a case of AML-MR involving unreported gene fusion.

CASE PRESENTATION: A 59-year-old female with multiple comorbidities presented with slurred speech. Pathological evaluation and DNA-based next-generation sequencing results were consistent with AML-MR. AML fluorescence in situ hybridization (FISH) panel revealed an extra signal for RUNX1. G-banding karyotype revealed a solitary rare t(X;21)(q26.1;q22.12) in 18 out of 20 cells analyzed. Optical genome mapping (OGM) was performed to precisely localize the breakpoints and identify the specific genes or gene fusions created by the translocation. OGM identified a novel fusion involving ENOX2 (Xq26.1) and RUNX1 (21q22.12), which was subsequently confirmed by a retrospective custom FISH probe targeting ENOX2.

CONCLUSIONS

The identification of an ENOX2::RUNX1 fusion in AML-MR expands the spectrum of rare RUNX1 fusions. High-resolution approaches such as OGM enable precise delineation of fusion partners and breakpoints beyond the resolution of conventional cytogenetics. While the biological and clinical significance of this fusion remains to be determined, this finding highlights the value of OGM in the identification of novel and rare genomic rearrangements in leukemia and other malignancies.