Acute Promyelocytic Leukemia Lacking the Classic Translocation t(15;17)

Introduction

Acute promyelocytic leukemia (APL) is a subtype of acute myeloid leukemia (AML) characterized by the reciprocal translocation t(15;17)(q22;q12) resulting in the fusion gene PML-RARA and an oncoprotein that impairs myeloid differentiation (Arber et al., 2008; de The et al., 1990; Rowley et al., 1977). Morphological and clinical characteristics include hypergranular leukemic promyelocytes, Auer rods, and coagulopathy. The use of all-trans retinoic acid (ATRA) has revolutionized the management of this disease that has become the most curable form of AML in adults (Castaigne et al., 1990; Tallman et al., 1997). In relapsed APL, arsenic trioxide can induce complete morphological, cytogenetic and molecular remission (Douer and Tallman, 2005; Soignet et al., 1998).
Cases lacking the classic t(15;17) are divided into two separate groups that behave differently and are now considered different disease entities (Arber et al., 2008). The first group represents cryptic and complex APL where t(15;17) is absent on routine cytogenetic studies but PML-RARA is present on molecular studies (Grimwade et al., 2000). This group shares the same phenotype, prognosis, and sensitivity to ATRA as classic APL, and is thus managed similarly. The second group, “AML with a variant RARA translocation”, is no longer considered part of APL and includes acute myeloid leukemias with translocations involving RARA and a variety of partner genes other than PML (Arber et al., 2008). Compared to classic APL, these leukemias often exhibit significant differences in malignant phenotype and sensitivity to ATRA which will be further explored in this chapter.
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