Molecular analysis and clinical outcome of adult APL patients with the type V PML-RAR alpha isoform: results from Intergroup protocol 0129

The type V (for (v) under bar ariable) promyelocytic leukemia retinoic acid receptor (PML-RAR)alpha transcript, found in approximately 8% of adult pat ients with acute promyelocytic leukemia (APL), is defined molecularly by tr uncation of PML exon 6 and frequent insertion of genetic material from RAR alpha intron 2, To more fully characterize the molecular features of PML-RA R alpha V-type transcripts and to determine whether V-form APL patients hav e a distinct clinical presentation or prognosis, we analyzed 18 adult V-for m APL patients enrolled on Intergroup protocol 0129 (INT-0129). Truncations in PML exon 6 ranged from 8 to 146 nucleotides, and 3 to 127 extra nucleot ides (1 to 42 extra amino acids) were inserted at the PML exon 6/RAR alpha exon 3 junction in 13 cases. No distinguishing morphologic, cytogenetic, or immunophenotypic features of V-form blasts were identified. A total of 5 o f 7 patients induced with ATRA and 8 of 11 patients who received chemothera py for induction achieved complete remission (CR), Six patients have relaps ed, 4 after chemotherapy induction and 2 after ATRA, Nine patients (50%) ar e alive, 6 in continuous CR, 2 after salvage therapy for relapsed or refrac tory disease, and 1 after alternative treatment following early removal fro m protocol, Although the failure rate for V-form APL patients was high (61% ), the low power of the current study to detect clinically significant diff erences precludes a meaningful comparison of clinical outcomes between the 18 V-form cases and non-V-form adult APL patients enrolled on INT-0129, (Bl ood, 2000;95:398-403) (C) 2000 by The American Society of Hematology.