Intron-exon structure of relevant PML and RARα gene regions and the generation of three PML-RARα mRNA types in APL. (DNA Level) Solid lines indicate introns and rectangles indicate exons. (□), exons preserved in all measured PML-RARα mRNA transcripts; (▪), exons excluded from all PML-RARα mRNA transcripts; (▧), exons present in L-form and V-form but not S-form PML-RARα mRNA transcripts. The vertical arrows indicate the three breakpoint cluster regions of the PML gene as follows: S-form (S) in intron 3 (bcr3); V-form (V), variably, in the distal half of exon 6 (bcr2); and L-form (L) in intron 6 (bcr1). The RARα gene is consistently broken in intron 2, labeled “All Sites.” (mRNA Level) Joined rectangles show how exons are spliced together to form three types of PML-RARα mRNA at the splice junctions indicated by the vertical arrows. The thin horizontal line below the rectangles indicates the sites of variable breakage in exon 6 in V-form cases. The thick horizontal line above the rectangles indicates the site of the oligonucleotide hybridization probe that spans the PML exon 6 RARα exon 3 junction in L-form cases. The arrowheads indicate the approximate sites of PCR primers used to amplify all three types of PML-RARα mRNA.