Acute Promyelocytic Leukemia: A History over 60 Years-From the Most Malignant to the most Curable Form of Acute Leukemia

Abstract

Acute promyelocytic leukemia (APL) is a distinct subtype of acute myeloid leukemia (AML) that is cytogenetically characterized by a balanced reciprocal translocation between chromosomes 15 and 17, which results in the fusion of the promyelocytic leukemia (PML) and retinoic acid receptor alpha (RARα) genes. Because patients with APL present a tendency for severe bleeding, often resulting in an early fatal course, APL was historically considered to be one of the most fatal forms of acute leukemia. However, therapeutic advances, including anthracycline- and cytarabine-based chemotherapy, have significantly improved the outcomes of APL patients. Due to the further introduction of all-trans retinoic acid (ATRA) and-more recently-the development of arsenic trioxide (ATO)-containing regimens, APL is currently the most curable form of AML in adults. Treatment with these new agents has introduced the concept of cure through targeted therapy. With the advent of revolutionary ATRA-ATO combination therapies, chemotherapy can now be safely omitted from the treatment of low-risk APL patients. In this article, we review the six-decade history of APL, from its initial characterization to the era of chemotherapy-free ATRA-ATO, a model of cancer-targeted therapy.

Keywords: Acute promyelocytic leukemia; All-trans retinoic acid; Arsenic trioxide; Chemotherapy; PML-RARA; Prognosis; Treatment.

Fig. 1

Highlights in the history of APL treatment

Fig. 2

APL was first described in 1957 by Leif Hillestad, who published three cases of a special type of AML in Acta Medica Scandinavica

Fig. 3

Morphologic variants of APL

Fig. 4

APL is characterized by a specific balanced reciprocal translocation t(15;17) that fuses the PML gene on chromosome 15 to the RARα gene on chromosome 17