Quantitative monitoring of the T315I mutation in patients with chronic myeloid leukemia (CML)

Leuk Res. 2009 Apr;33(4):551-5. doi: 10.1016/j.leukres.2008.08.018. Epub 2008 Sep 30.

Abstract

Tyrosine kinase inhibitors (TKIs) have dramatically improved the treatment of chronic myeloid leukemia (CML). However, resistances are occasionally observed, mainly due to mutations within the BCR-ABL kinase domain. The T315I substitution confers complete resistance to TKIs commonly used in clinical practice. In the present study, we used an allele-specific quantitative-RT-PCR to perform a molecular follow-up of BCR-ABL transcripts harboring the T315I mutation. We retrospectively quantified BCR-ABL315I mRNA in five patients who acquired the T315I mutation. Our results highlight the relevance of allele-specific Q-RT-PCR experiments for the monitoring of mutated BCR-ABL transcripts and suggest that the kinetics of emergence of T315I mutant mRNA is influenced by the stage of the disease and the presence of previous BCR-ABL kinase domain mutations.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Drug Resistance, Neoplasm / genetics*
  • Female
  • Fusion Proteins, bcr-abl / genetics*
  • Humans
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / drug therapy
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / genetics*
  • Male
  • Mutation
  • Protein Kinase Inhibitors / therapeutic use
  • RNA, Messenger / analysis
  • Retrospective Studies
  • Reverse Transcriptase Polymerase Chain Reaction

Substances

  • Protein Kinase Inhibitors
  • RNA, Messenger
  • Fusion Proteins, bcr-abl