Detection of minimal residual disease in patients with AML1/ETO-associated acute myeloid leukemia using a novel quantitative reverse transcription polymerase chain reaction assay

Leukemia. 1998 Sep;12(9):1482-9. doi: 10.1038/sj.leu.2401128.

Abstract

The AML1/ETO fusion transcript can be detected by reverse transcription polymerase chain reaction (RT-PCR) in patients with t(8;21)-associated acute myeloid leukemia (AML) in long-term complete remission (CR). Quantitation of the amount of the fusion transcript during CR may therefore be more predictive of cure or relapse than a simple qualitative assessment. Real Time PCR, a fluorometric-based technique, allows simple and rapid quantitation of a target sequence during the extension phase of PCR amplification, in contrast to end-point quantitative methods. Six patients with t(8;21)(q22;q22) AML, who achieved CR were studied by Real Time RT-PCR at different time intervals following diagnosis and high-dose cytarabine and anthracycline-based induction therapy. Five patients had a diagnostic bone marrow (BM) sample available for molecular analysis. Each patient showed > or = 10(3) copies of the AML1/ETO fusion transcript at diagnosis, and each showed a 2- to 4-log decrease in copy number following successful induction chemotherapy. This is comparable to the log-fold reduction in leukemic blasts that is thought to occur in patients successfully cytoreduced into CR by induction chemotherapy. The sixth patient showed a relatively high copy number immediately following successful remission induction chemotherapy, which continued to increase during early CR and was later followed by relapse. Real Time RT-PCR appears to offer advantages over previously used quantitative RT-PCR methods by providing absolute quantitation of the target sequence, expanding the dynamic range of quantitation to over six orders of magnitude, eliminating the post-PCR processing, and reducing labor and carryover contamination. These features make this an attractive method to prospectively evaluate the prognostic value of AML1/ETO fusion transcript quantitation in a larger patient population with t(8;21)(q22;q22) AML in CR.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Acute Disease
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Chromosomes, Human, Pair 21 / genetics
  • Chromosomes, Human, Pair 8 / genetics
  • Core Binding Factor Alpha 2 Subunit
  • Feasibility Studies
  • Humans
  • Leukemia, Myeloid, Acute / diagnosis*
  • Leukemia, Myeloid, Acute / drug therapy
  • Leukemia, Myeloid, Acute / genetics
  • Neoplasm, Residual
  • Oncogene Proteins, Fusion*
  • Polymerase Chain Reaction / methods*
  • RUNX1 Translocation Partner 1 Protein
  • Recombinant Fusion Proteins / analysis
  • Remission Induction
  • Transcription Factors / analysis*
  • Translocation, Genetic / genetics

Substances

  • AML1-ETO fusion protein, human
  • Core Binding Factor Alpha 2 Subunit
  • Oncogene Proteins, Fusion
  • RUNX1 Translocation Partner 1 Protein
  • Recombinant Fusion Proteins
  • Transcription Factors