Molecular Remission in Acute Promyelocytic Leukemia: An Analysis of the PML/RARα Fusion Gene and Its Application to Minimal Residual Disease Detection

Background and Purpose: Acute promyelocytic leukemia (APL) is a well-defined subtype of acute myelogenous leukemia (AML) characterized by the presence of a specific PML/RARα fusion gene resulting from a unique chromosomal translocation t(15;17). The translocation yields a PML/RARα gene that is transcribed in a fusion PML/RARα mRNA. The PML/RARα fusion transcript can be illustrated in APL by a specific reverse-transcription polymerase chain reaction (RT-PCR). The purpose of this study was to monitor minimal residual disease (MRD) with RT-PCR in APL and compare the findings with clinical (morphological and cytogenetic) analysis of the disease. Methods: To access the presence of MRD in APL, we examined bone marrow aspirates of 14 patients with APL using RT-PCR followed by nested PCR amplification to detect the presence of PML/RARα gene during the course of their disease. Results: All patients had a positive test result for 1 of the 2 PML/RARα isoforms at diagnosis or during relapse. All patients achieved morphologic and cytogenetic remission after first-induction chemotherapy with all-trans retinoic acid. Twelve patients achieved molecular remission after first-induction chemotherapy, whereas 2 patients were PCR positive for PML/RARα chimeric sequence. Eventually, all patients achieved and remained in morphologic, cytogenetic, and molecular remission in this ongoing study. Conclusion: The diagnosis of APL depends primarily on morphological and cytogenetic recognitions. Our data indicate that RT-PCR provides the most sensitive and accurate diagnostic information in APL.