A rare case of variant acute promyelocytic leukemia with fusion gene: case report and literature review.

Acute promyelocytic leukemia (APL) is a distinct subtype of acute myeloid leukemia characterized by the promyelocytic leukemia-retinoic acid receptor alpha () fusion gene and exceptional responsiveness to differentiation therapy with all-trans retinoic acid (ATRA) and arsenic trioxide (Arsenic Trioxide). However, rare variant forms of APL involving alternative fusion partners, such as , are typically resistant to ATRA/ATO-based regimens and are associated with poor clinical outcomes. We report a rare case of -positive APL in a patient who initially presented with clinical, morphological, and immunophenotypic features consistent with classical APL. Standard diagnostic evaluations, including morphology, flow cytometry, and fluorescence in situ hybridization (FISH), failed to detect the fusion abnormality. The diagnosis was ultimately confirmed by RNA sequencing (RNA-Seq). Empirical induction with ATRA and ATO was initiated but resulted in persistent and progressive promyelocytosis. Anthracycline-based chemotherapy was subsequently administered, followed by azacitidine combined with venetoclax in the subsequent course of treatment. Although partial hematologic improvement was observed, the overall response remained suboptimal. This case underscores the diagnostic challenges of atypical APL and highlights the pivotal role of RNA-Seq in identifying cryptic rearrangements. A literature review suggests that -positive APL represents a biologically and clinically distinct entity with highly variable treatment responses and poor prognosis. Early molecular diagnosis and prompt implementation of conventional chemotherapy or targeted therapies such as venetoclax may be essential to improving outcomes in this rare APL subtype.