Work

A novel PML::RARA fusion in acute promyelocytic leukemia: a case report and literature review

Year: 2026

Type: article

Abstract: Acute promyelocytic leukemia (APL) is a distinct subtype of acute myeloid leukemia defined by the t(15;17)(q24;q21)-derived PML::RARA fusion. However, a small subset of patients harbor cryptic or atypical RARA rearrangements that escape detection by routine real-time quantitative RT-PCR (qRT-PCR). We report a 34-year-old man presenting typical APL in whom repeated testing for the canonical long, short, and variant PML::RARA transcripts yielded negative results. RNA sequencing subsequently identified a previously unreported in-frame fusion linking PML exon 8 to a 58–base pair–deleted RARA exon 3. The resulting chimeric transcript retained the PML coiled-coil domain as well as the DNA- and ligand-binding domains of RARA , suggesting preserved sensitivity to retinoid-based therapy. Consistent with this prediction, induction therapy with all-trans retinoic acid (ATRA) and arsenic trioxide (ATO) resulted in achievement of complete molecular remission. Molecular relapse occurred three months after premature discontinuation of maintenance therapy, underscoring the leukemogenic potential of this novel fusion. This observation expands the molecular spectrum of APL and highlights the potential value of incorporating RNA sequencing into the diagnostic workflow for morphologically suspected but PCR-negative APL.

Source: Frontiers in Oncology

DOI: 10.3389/fonc.2026.1784103