Acute promyelocytic leukemia (APL) is characterized cytogenetically by the t(15;17)(q22;qll-21) translocation. To compare molecular events among pediatric and adult APL cases, we designed two sets of oligonucleotide primers using published cDNA sequence for PML/RARα fusion transcripts, and undertook reverse transcriptase-polymerase chain reaction (RT-PCR) analysis of 22 US pediatric cases of APL. PML/RARα fusion transcripts were detected in all APL cases, including two cases lacking cytogenetic evidence of t(15;17). Breakpoint usage in PML was determined using a combination of PCR amplification with differing 5' primers, junction-specific probes, and sequence analysis in selected cases. Consistent with previously published data, case analysis demonstrated fusion products resulting from three breakpoint cluster regions (bcr) in PML, and a single breakpoint region in intron 2 of RARα. Transcripts resulting from breakpoints in bcr1 were detected in 59% of cases, bcr2 in 27% and bcr3 in 14%. This distribution is dissimilar to that observed in adults, where bcr2 comprises a lesser and bcr3 a greater portion of cases. These results suggest that the pathogenesis of the t(15;17) in APL may differ among patient sets. RT-PCR with these primer sets is a reliable method for detecting PML/RARα chimeric transcript in t(15;17) containing APL.