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Acute promyelocytic leukemia (PML) is characterized by a reciprocal translocation between chromosomes 15 and 17 resulting in a chimeric PML and retinoic acid receptor alpha (RARA) oncogene. The resultant fusion protein (PML/RARA) is thought to block differentiation of bone marrow cells arrested at the promyelocytic stage. In vitro and in vivo studies have shown that the large majority of APL cells undergo granulocytic maturation after ATRA therapy. We report a unique case of a PML/RARA positive APL patient exhibiting extensive monocytic differentiation after ATRA therapy as documented by morphology, flow cytometry, and FISH studies. We discuss potential dual capability for granulocytic/monocytic differentiation of PML/RARA positive APL cells and implications of monocytic differentiation in the management of APL patients treated with ATRA.

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