Four-channel asymmetric Real-Time PCR hybridization probe assay: a rapid pre-screening method for critical BCR-ABL kinase domain mutations

Clin Biochem. 2012 Mar;45(4-5):345-51. doi: 10.1016/j.clinbiochem.2011.12.026. Epub 2012 Jan 12.

Abstract

Objectives: Within the laboratory protocols, used for the study of BCR-ABL resistance mutations in chronic myeloid leukemia patients treated with Imatinib, direct sequencing remains the reference method. Since the incidence of patients with a mutation-related loss of response is not very high, it is very useful in the routine laboratory to perform a fast pre-screening method.

Design and methods: With this in mind, we have designed a new technique, based on a single Real-Time FRET-based PCR, followed by a study of melting peaks. This new tool, developed in a LightCycler 2.0, combines four different fluorescence channels for the simultaneous detection, in a single close tube, of critical mutations within the ABL kinase domain.

Results: Assay evaluation performed on 33 samples, previously genotyped by sequentiation, resulted in full concordance of results.

Conclusions: This new methodology detects in a few steps the presence of critical mutations associated to Imatinib resistance.

Publication types

  • Validation Study

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antineoplastic Agents / therapeutic use*
  • Base Sequence
  • Benzamides
  • Bone Marrow / metabolism
  • DNA Mutational Analysis / methods
  • DNA Probes / chemistry
  • DNA Probes / metabolism*
  • Drug Resistance, Neoplasm*
  • Female
  • Fluorescence Resonance Energy Transfer
  • Fusion Proteins, bcr-abl / blood
  • Fusion Proteins, bcr-abl / chemistry
  • Fusion Proteins, bcr-abl / genetics
  • Fusion Proteins, bcr-abl / metabolism*
  • Humans
  • Imatinib Mesylate
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / blood
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / drug therapy*
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / metabolism
  • Male
  • Middle Aged
  • Multiplex Polymerase Chain Reaction
  • Mutation*
  • Nucleic Acid Denaturation
  • Piperazines / therapeutic use*
  • Pyrimidines / therapeutic use*
  • Real-Time Polymerase Chain Reaction
  • Retrospective Studies

Substances

  • Antineoplastic Agents
  • Benzamides
  • DNA Probes
  • Piperazines
  • Pyrimidines
  • abl-bcr fusion protein, human
  • Imatinib Mesylate
  • Fusion Proteins, bcr-abl