Clinical and cytogenetic features of acute promyelocytic leukemia

Acute promyelocytic leukemia (APL) is an acute myeloid leukemia (AML) characterized by a differentiation block of the granulocytic lineage at the promyelocytic stage. APL accounts for 10 to 15% of AML. In the absence of treatment, its clinical outcome is poor due to the unpredictable occurrence of lethal hemorrhages. In the FAB classification, APL corresponds to M3-AML, characterized by blast cells with heavy azurophilic granules, Auer rods, and a reniform or bilobed nucleus (Figure 70.1). APL is rarely associated with large circulating tumor cell burden, despite its ability to completely invade the bone marrow.

Molecularly, more than 95% of APL is associated with the balanced reciprocal translocation t(15;17)(q22;q11–12), leading to fusion of the promyelocytic gene (PML) on chromosome 15 with the retinoic-acid receptor alpha gene (RARA) on chromosome 17. The remaining APL patients present alternative translocations, always involving RARA. Among these variants, the most common is the t(11;17) translocation that fuses the promyelocytic leukemia zinc finger (PLZF) gene to RARA (1).