Acute promyelocytic leukemia (APL) is a clinically and genetically distinct subtype of AML caused by fusion of the promyelocytic leukemia (PML) gene, on chromosome 15, with the retinoic acid receptor a (RARA) gene, on chromosome 17. The fusion of PML (or one of the rare variant partner genes) with RARA results in a hybrid protein (PML-RARA) that interferes with function of both the wild-type PML and RARA genes. The end result is a block in myeloid differentiation, disruption of cellular growth control, and development of clinical APL. The disease was first described clinically in 195 7,1 and the classic reciprocal chromosomal translocation [t(15;17)(q22;q21)] that characterizes APL was identified by Rowley et al. in 1977.2 Almost three decades later, the molecular pathogenesis of APL is reasonably well understood,3 and modern treatment regimens have been developed that lead to the cure of more than 70% patients. From a clinical perspective, the challenge is to further increase this cure rate, while reducing (or eliminating) side effects and long-term toxicities associated with intensive chemotherapy. Well-designed clinical trials continue to be the best option for most patients with APL, for it is only in the context of such trials that clinicians can learn how to safely de-escalate therapy in low-risk patients while maintaining excellent outcomes in patients who present with higher risk disease.

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