PML mutational analysis in APL. (A) SSCP (top panels) and sequencing analysis (2 middle panels, with the mutated sequences on the upper middle panel) identified 2 DNA sequence variations (arrows) predicted to result in a truncated PML protein (bottom panels) among the 17 APL RA-resistant samples. The first is a small deletion (1272delAG) and the second a splice site mutation (IVS3 - 1G → A). (B) PML missense, truncating, and silent mutations in hematopoietic malignancies. The schematic structure of the PML protein is shown: P indicates proline-rich region; R, RING finger domain; B1 and B2, B-boxes 1 and 2; NLS, nuclear localization signal; M, sumoylation sites. The 1272delAG is indicated as Mut 1 and IVS3 - 1G → A as Mut 2. The polymorphic mutation is also indicated.