Efficacy of Fluorescence In Situ Hybridization for Detecting PML/RARA Gene Fusion in Treated and Untreated Acute Promyelocytic Leukemia

To test the efficacy of fluorescence in situ hybridization (FISH) for detection of fusion of the promyelocytic leukemia (PML) and retinoic acid receptor alpha (RARA) genes in patients with treated or untreated acute promyelocytic leukemia (APL). We conducted a retrospective blind study on a series of stored bone marrow specimens from normal subjects and patients with APL. Conventional cytogenetic and FISH analyses were done on interphase and metaphase cells in specimens from 31 normal subjects and 19 patients with untreated or treated APL. From 25 of the normal specimens, we calculated a normal cutoff of 10% for interphase cells and 0% for metaphase cells. With use of these criteria, the other six specimens from normal subjects showed normal findings, and each of the seven specimens from patients with untreated APL was abnormal by FISH analysis. The specimens from four patients in clinical relapse or with residual APL were abnormal. Of the eight specimens from patients in clinical remission, three were abnormal; two of these patients had a relapse within 8 months, and the other patient had received 1 month of chemotherapy and was entering remission. Of the other five patients in remission, four had normal FISH results and have now been in remission for 2.5 to 10 years. The other patient in remission with normal FISH results had a relapse within 6 months. PML/RARA fusion was detectable in three patients with hypogranular APL and in three with a cytogenetic variant of the t(15;17). The results of this study suggest that FISH with PML and RARA probes can be used to diagnose APL and may be useful for monitoring treated patients.