Acute promyelocytic leukemia: clinical relevance of two major PML-RAR alpha isoforms and detection of minimal residual disease by retrotranscriptase/polymerase chain reaction to predict relapse

Blood. 1993 Aug 15;82(4):1264-9.

Abstract

Recent data have shown that the PML-RAR alpha fusion gene resulting from translocation t(15;17) is a highly reliable molecular marker of acute promyelocytic leukemia (APL). In this study performed on 97 Chinese patients with APL, the retrotranscriptase/polymerase chain reaction (RT/PCR) was used to evaluate the clinical relevance of the long (L) or short (S) PML-RAR alpha fusion mRNA isoforms and to study minimal residual disease during clinical remission (CR). There were more early deaths during the all-trans retinoic acid (ATRA) induction treatment and more relapses within 2 years of CR in the S-type (6 of 19 cases) than in the L-type group (2 of 33 cases) (P < .025). Among 12 cases analyzed before and after the ATRA-induced CR, 9 cases (75%) showed positive RT/PCR, whereas only 3 cases showed a negative result, justifying the need for chemotherapy after ATRA-induced CR. Eleven of 62 APL patients in CR, after ATRA-induced CR and chemotherapy consolidation (follow-up, from 3 to 72 months), showed positive RT/PCR. Five of them relapsed within 1 to 6 months after the positive test; one converted to negative after further chemotherapy; and 5 remained in CR status without further PCR data. However, the latter 5 cases all received further intensive consolidation therapy after the PCR positivity. These results show that a positive RT/PCR of PML-RAR alpha is a sensitive predictor of relapse in APL.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Base Sequence
  • Carrier Proteins / genetics*
  • Child
  • Child, Preschool
  • Chromosomes, Human, Pair 15
  • Chromosomes, Human, Pair 17
  • Cloning, Molecular
  • Female
  • Humans
  • Leukemia, Promyelocytic, Acute / diagnosis*
  • Leukemia, Promyelocytic, Acute / genetics
  • Male
  • Middle Aged
  • Molecular Sequence Data
  • Neoplasm Proteins*
  • Nuclear Proteins*
  • Oncogene Proteins, Fusion / genetics*
  • Polymerase Chain Reaction*
  • Promyelocytic Leukemia Protein
  • Receptors, Retinoic Acid
  • Recurrence
  • Transcription Factors / genetics*
  • Translocation, Genetic
  • Tumor Suppressor Proteins

Substances

  • Carrier Proteins
  • Neoplasm Proteins
  • Nuclear Proteins
  • Oncogene Proteins, Fusion
  • Promyelocytic Leukemia Protein
  • Receptors, Retinoic Acid
  • Transcription Factors
  • Tumor Suppressor Proteins
  • PML protein, human