Feasibility and clinical significance of real-time quantitative RT-PCR assay of PML-RARalpha fusion transcript in patients with acute promyelocytic leukemia

Hematol J. 2001;2(5):330-40. doi: 10.1038/sj.thj.6200128.

Abstract

Introduction: To study the relationship between the expression level of the PML-RARalpha fusion transcripts and the clinical status and efficiency of the therapy in acute promyelocytic leukemia (APL) patients, we applied a very sensitive and specific real-time Reverse Transcription Polymerase Chain Reaction (RT-PCR) system to quantify the dose of PML-RARalpha fusion transcripts in a series of APL patients at distinct disease stages.

Materials and methods: A total of 31 APL patients (19 males and 12 females; aged from 8 to 74 years) from eight hospitals in Shanghai were analysed. Real-time Quantitative RT-PCR was used to measure the normalized dose (DoseN) of PML-RARalpha fusion transcripts.

Results: A wide range of PML-RARalpha DoseN above 1 x 10(3) was noted in 25 newly diagnosed patients. PML-RARalpha DoseN was significantly decreased after remission induction with ATRA, ATRA/chemotherapy or As2O3 and further reduced after consolidation. The fact that all patients with long disease free survival had a constantly low PML-RARalpha DoseN below 2 x 10(2) and a higher level predicted impending relapse suggests that this value could serve as a 'threshold' for molecular remission. PML-RARalpha DoseN was also of prognostic value in a group of relapsed patients, since good response to As2O3 reinduction was accompanied by a remarkable reduction of fusion transcript level, whereas patients with high PML-RARalpha Dose(N) after the second CR tended to relapse again rapidly.

Conclusion: These results confirm that real-time RT-PCR assay for PML-RARalpha transcripts in APL patients is useful in reflecting leukemic burden, assessing response to treatment and indicating the ultimate clinical outcome or curability of disease.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Antineoplastic Agents / administration & dosage
  • Bone Marrow / pathology
  • Child
  • Disease Progression
  • Disease-Free Survival
  • Feasibility Studies
  • Female
  • Humans
  • Leukemia, Promyelocytic, Acute / diagnosis*
  • Leukemia, Promyelocytic, Acute / drug therapy
  • Leukemia, Promyelocytic, Acute / genetics
  • Male
  • Middle Aged
  • Neoplasm Proteins / analysis*
  • Neoplasm Proteins / genetics
  • Neoplasm, Residual / diagnosis
  • Neoplasm, Residual / genetics
  • Oncogene Proteins, Fusion / analysis*
  • Oncogene Proteins, Fusion / genetics
  • Prognosis
  • RNA, Messenger / analysis
  • Reproducibility of Results
  • Reverse Transcriptase Polymerase Chain Reaction / standards*
  • Sensitivity and Specificity

Substances

  • Antineoplastic Agents
  • Neoplasm Proteins
  • Oncogene Proteins, Fusion
  • RNA, Messenger
  • promyelocytic leukemia-retinoic acid receptor alpha fusion oncoprotein