Rapid automated detection of ABL kinase domain mutations in imatinib-resistant patients

Cancer Lett. 2011 Dec 22;312(2):228-34. doi: 10.1016/j.canlet.2011.08.009. Epub 2011 Aug 22.

Abstract

ABL tyrosine kinase inhibitor (TKI), imatinib is used for BCR-ABL(+) leukemias. We developed an automatic method utilizing guanine-quenching probes (QP) to detect 17 kinds of mutations frequently observed in imatinib-resistance. Results were obtained from 100μL of whole blood within 90min by this method. Detected mutations were almost identical between QP method and direct sequencing. Furthermore, the mutation-biased PCR (MBP) was added to the QP method to increase sensitivity, resulting earlier detection of T315I mutation which was insensitive to any ABL TKIs. Thus, the QP and MBP-QP may become useful methods for the management of ABL TKI-treated patients.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Antineoplastic Agents / therapeutic use*
  • Automation*
  • Benzamides
  • Child
  • Child, Preschool
  • Drug Resistance, Neoplasm
  • Female
  • Humans
  • Imatinib Mesylate
  • Male
  • Middle Aged
  • Mutation*
  • Piperazines / therapeutic use*
  • Polymerase Chain Reaction
  • Proto-Oncogene Proteins c-abl / genetics*
  • Pyrimidines / therapeutic use*
  • Young Adult

Substances

  • Antineoplastic Agents
  • Benzamides
  • Piperazines
  • Pyrimidines
  • Imatinib Mesylate
  • Proto-Oncogene Proteins c-abl