Real-time PCR analysis of PML-RAR alpha in newly diagnosed acute promyelocytic leukaemia patients treated with arsenic trioxide as a front-line therapy

Ann Oncol. 2006 Oct;17(10):1553-9. doi: 10.1093/annonc/mdl150. Epub 2006 Jul 10.

Abstract

Background: Recently, patients with acute promyelocytic leukaemia (APL) have experienced significant clinical gains after treatment with arsenic trioxide. However, the use of this agent as a front-line therapy for newly diagnosed patients is unclear.

Patients and methods: Of 95 newly diagnosed APL patients, 85 patients who achieved complete remission (CR) were sequentially evaluated during a 4-60 month period by conventional RT-PCR. A total of 30 patients (six relapsed and 24 in continued CR) were selected and monitored by quantitative real-time PCR (RQ-PCR) assay. The PML-RARalpha fusion transcripts values were normalised to every 10(6) copies of G6PDH transcripts (NQ).

Results: RQ-PCR analyses showed a rapid rate of clearance of NQ levels during the courses of arsenic therapy. In the majority of patients in CR, the NQ levels were below 5 x 10(2) in peripheral blood (PB) samples. In all the relapsed cases with follow-up intervals of 1-6 months (median 3 months) clinical relapse was predictable by increasing NQ level above this threshold.

Conclusions: Our study highlights the usefulness of PB and the definition of threshold level for early prediction of relapse. The threshold level correlates well with risk of relapse; therefore, transcript ratio below the level should be regarded as a goal in the clinical management of this disease.

Publication types

  • Evaluation Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Antineoplastic Agents / therapeutic use
  • Arsenic Trioxide
  • Arsenicals / therapeutic use*
  • Biomarkers, Tumor / analysis
  • Biomarkers, Tumor / metabolism
  • Child
  • Early Diagnosis
  • Female
  • Follow-Up Studies
  • Gene Expression / drug effects
  • Glucosephosphate Dehydrogenase / metabolism
  • Humans
  • Leukemia, Promyelocytic, Acute / drug therapy*
  • Leukemia, Promyelocytic, Acute / metabolism
  • Leukemia, Promyelocytic, Acute / pathology
  • Male
  • Middle Aged
  • Multivariate Analysis
  • Neoadjuvant Therapy / methods
  • Oncogene Proteins, Fusion / analysis*
  • Oncogene Proteins, Fusion / metabolism
  • Oxides / therapeutic use*
  • Protein Isoforms / analysis
  • Protein Isoforms / metabolism
  • Recombinant Fusion Proteins / analysis
  • Recombinant Fusion Proteins / metabolism
  • Recurrence
  • Reverse Transcriptase Polymerase Chain Reaction / methods*

Substances

  • Antineoplastic Agents
  • Arsenicals
  • Biomarkers, Tumor
  • Oncogene Proteins, Fusion
  • Oxides
  • Protein Isoforms
  • Recombinant Fusion Proteins
  • promyelocytic leukemia-retinoic acid receptor alpha fusion oncoprotein
  • Glucosephosphate Dehydrogenase
  • Arsenic Trioxide