A previously healthy 48-year-old woman presented with recurrent mucocutaneous infections. Her complete blood count showed white blood cells, 17.4 × 10⁹/L; hemoglobin, 102 g/L; and platelets, 16 × 10⁹/L, with 42% blasts. D-dimers were <20 mg/dL. A peripheral blood smear showed undifferentiated blasts with round to slightly irregular nuclei with fine chromatin, scant agranular cytoplasm (panel A; original magnification ×100; Giemsa stain), and rare Auer rods (panels B-C; solid arrows; original magnification ×100; Giemsa stain). Flow cytometry showed bright CD34⁺ blasts (panel E) within the classic blast gate defined by low side scatter/intermediate CD45 expression (panel D). The blasts also expressed CD117, heterogeneous CD13, partial CD2, and partial CD56 (not shown). Despite the bright CD34 expression and lack of typical morphology, the possibility of acute promyelocytic leukemia (APL) was considered with bright myeloperoxidase (MPO) expression (flow cytometry [panel F] and enzyme cytochemistry [panel G; original magnification ×100]). RNA polymerase chain reaction showed a bcr3-associated short PML-RARA fusion transcript, and next-generation sequencing identified FLT3–internal tandem duplication (FLT3-ITD) and 2 point mutations (FLT3c. 2503G>T, p.D835Y and FLT3c. 2504A>T, p.D835V). Bone marrow was inaspirable, but core biopsy and touch preparations showed undifferentiated leukemic blasts, including some bilobed forms.

APL with the bcr3 isoform of PML-RARA is associated with FLT3-ITD, immature morphology, hyperleukocytosis, and coexpression of CD34, CD2, and CD56. This case highlights the importance of keeping APL in the differential in cases with immature, blast-like morphology but with a constellation of antigen expression including CD34, CD2, CD56, and bright MPO.