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

James L. Slack, Cheryl L. Willman, Janet W. Andersen, Yun Ping Li, David S. Viswanatha, Clara D. Bloomfield, Martin S. Tallman, Robert E. Gallagher

Research output: Contribution to journalArticlepeer-review

51 Scopus citations

Abstract

The type V (for variable) promyelocytic leukemia retinoic acid receptor (PML-RAR)α transcript, found in approximately 8% of adult patients with acute promyelocytic leukemia (APL), is defined molecularly by truncation of PML exon 6 and frequent insertion of genetic material from RARα intron 2. To more fully characterize the molecular features of PML-RARα V-type transcripts and to determine whether V-form APL patients have a distinct clinical presentation or prognosis, we analyzed 18 adult V-form 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 nucleotides (1 to 42 extra amino acids) were inserted at the PML exon 6/RARα exon 3 junction in 13 cases. No distinguishing morphologic, cytogenetic, or immunophenotypic features of V-form blasts were identified. A total of 5 of 7 patients induced with ATRA and 8 of 11 patients who received chemotherapy for induction achieved complete remission (CR). Six patients have relapsed, 4 after chemotherapy induction and 2 after ATRA. Nine patients (50%) are alive, 6 in continuous CR, 2 after salvage therapy for relapsed or refractory disease, and 1 after alternative treatment following early removal from protocol. Although the failure rate for V-form APL patients was high (61%), the low power of the current study to detect clinically significant differences precludes a meaningful comparison of clinical outcomes between the 18 V-form cases and non-V-form adult APL patients enrolled on INT-0129.

Original languageEnglish (US)
Pages (from-to)398-403
Number of pages6
JournalBlood
Volume95
Issue number2
StatePublished - Jan 15 2000

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

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