DOI: https://doi.org/10.36347/sjmcr.2026.v14i03.049

Pages: 516-520

Acute promyelocytic leukemia (APL) is a distinct subtype of acute myeloid leukemia usually associated with the t(15;17) (q24 ; q21) translocation and the PML-RARA fusion gene. Rare variant forms lacking this rearrangement may evade conventional cytogenetic detection, present with atypical morphology, and pose significant diagnostic and therapeutic challenges despite the hematologic emergency nature of APL. We report a 67-year-old man admitted for fever, weight loss, and severe bilateral epistaxis. Laboratory evaluation revealed anemia, marked hyperleukocytosis, and coagulation abnormalities consistent with disseminated intravascular coagulation. Peripheral blood smear showed 92% hypogranular blasts with occasional bilobed nuclei and rare Auer rods; myeloperoxidase cytochemistry demonstrated characteristic bundles. Immunophenotyping confirmed a myeloid phenotype with absence of CD34 and HLA-DR expression. Conventional karyotyping and fluorescence in situ hybridization were normal, whereas next-generation sequencing identified FLT3, IDH1, and NRAS mutations without evidence of PML-RARA fusion. Initial treatment with all-trans retinoic acid and corticosteroids was followed by azacitidine and venetoclax due to lack of response. This case underscores the diagnostic complexity of PML-RARA-negative APL-like presentations and highlights the essential role of advanced molecular techniques in guiding appropriate therapeutic decisions.