Acute promyelocytic leukemia: pathophysiology and clinical results update

Introduction Acute promyelocytic leukemia (APL) is a distinct subset of acute myeloid leukemia (AML) associated with unique features and requiring specific management. The disease was initially recognized in 1957 by Hillestad, who described three patients with a rapidly fatal acute leukemia characterized by an abundant number of abnormal promyelocytes infiltrating the marrow and a severe hemorrhagic syndrome. In the following decades, APL has become a well-recognized entity, characterized as the M3 subtype of AML within the French–American–British (FAB) morphologic classification accounting for approximately 10% of cases of AML. Clinically, APL is associated with a bleeding diathesis due to excessive fibrinolysis, which worsens during initial administration of chemotherapy. Most patients present with a low white blood cell (WBC) count, but 10% to 30% have a WBC count greater than 10,000/μL, with increased risk of serious and potentially fatal hemorrhages into the central nervous system and lungs. The disease is initiated by a malignant transformation of an immature myeloid cell followed by block in differentiation at the promyelocyte stage. The promyelocytes and blasts in > 95% of APL cases harbor a balanced, reciprocal translocation involving the long arms of chromosomes 15 and 17 that is often the only cytogenetic abnormality present. In spite of being an infrequent disease, APL represents one of the most successful examples of translational research in medicine. Over the past two decades, considerable progress has been made in the treatment of this leukemia, such that it has been converted nowadays into the most frequently curable adult leukemia.