Assessment and follow-up of the proportion of T315I mutant BCR-ABL transcripts can guide appropriate therapeutic decision making in CML patients

Leuk Res. 2005 Sep;29(9):1073-7. doi: 10.1016/j.leukres.2005.02.006. Epub 2005 Mar 23.

Abstract

Quantitative monitoring of imatinib mesylate (IM)-resistant, mutated BCR-ABL(+) cells during the follow-up of CML could be useful for optimizing therapeutic management. We retrospectively analyzed T315I mutated BCR-ABL clones throughout the CML history of two patients by nested-PCR-RFLP. At the time of progression, the T315I mutation represented 100% of the BCR-ABL transcripts. During follow-up, we showed that (i) despite a molecular response to IM, a high proportion of T315I transcripts were present (>85%) and predictive of relapse, (ii) interruption of IM and switching to other therapies resulted in a significant reduction in mutant transcript level while total BCR-ABL(+) transcripts remained stable.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Base Sequence
  • Benzamides
  • DNA Primers
  • Drug Monitoring
  • Follow-Up Studies
  • Fusion Proteins, bcr-abl / genetics*
  • Humans
  • Imatinib Mesylate
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / drug therapy*
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / genetics*
  • Mutation
  • Piperazines / therapeutic use*
  • Polymerase Chain Reaction
  • Polymorphism, Restriction Fragment Length
  • Pyrimidines / therapeutic use*
  • RNA, Messenger / genetics*
  • Retrospective Studies

Substances

  • Benzamides
  • DNA Primers
  • Piperazines
  • Pyrimidines
  • RNA, Messenger
  • Imatinib Mesylate
  • Fusion Proteins, bcr-abl