Coexistence of PML–RARα and BCR–ABL in acute promyelocytic leukemia

Abstract

Acute promyelocytic leukemia (APL) is a biologically distinct form of acute myeloid leukemia (AML), characterized by a translocation of the retinoic acid receptor α (RAR α ) gene on chromosome 17 [1]. Over 95% of cases result from t(15;17) (q22;q21), which allows fusion of the promyelocytic leukemia (PML) gene on chromosome 15 to RAR α , although a small minority of cases arise from variant translocations including t(11;17) and t(5;17) [1]. RAR α is believed to be important in the proliferation and diff erentiation of promyelocytes into neutrophils, and thus APL is characterized by the halting of granulocytes at the promyelocytic stage of diff erentiation in the bone marrow and peripheral blood. Also unique to APL compared to other forms of myeloid leukemia is the dramatic improvement in response with the use of diff erentiation agents. Th e combination of all- trans retinoic acid (ATRA) and arsenic trioxide (ATO), with or without chemotherapy, has achieved complete remission rates of 95% with 2-year overall survival 90% [2,3]. Th e prognosis of APL with additional cytogenetic abnormalities has also been studied. De Botton et al . [4] reported on the prognostic signifi cance of secondary chromosomal changes in 292 patients treated with ATRA and chemotherapy, fi nding no signifi cant diff erence in complete remission, event-free survival, relapse or overall survival at 2 years between patients with t(15;17) alone and those with other cytogenetic abnormalities. Twenty-six percent of patients included in this study were found to have additional chromosomal abnormalities, the most common of which was trisomy 8 in 45% of patients, followed by deletions or translocations involving chromosomes 9, 7, 21 and 17 [4]. In 2010, Cervera et al . [5] published data on 495 patients with APL treated with ATRA and chemotherapy, fi nding a similar overall rate of additional chromosomal abnormalities (28%), again with trisomy 8 as the most frequently noted. Similar complete remission rates were again observed, although patients with additional cytogenetic abnormalities had higher rates of coagulopathy, lower platelet counts and higher relapse-risk scores compared to those with t(15;17) alone [5]. Although additional cytogenetic abnormalities were signifi cantly associated with lower relapse-free survival, they were not identifi ed as independent risk factors for relapse [5].