Assessment and follow-up of the proportion of T315I mutant BCR-ABL transcripts can guide appropriate therapeutic decision making in CML patients.
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.
Hayette
Sandrine
S
Laboratoire d'ématologie et de Cytogénétique, Centre Hospitalier Lyon Sud, Pierre-Bénite, France.
Michallet
Mauricette
M
Baille
Marie-Laurence
ML
Magaud
Jean-Pierre
JP
Nicolini
Franck E
FE
D001483:Base Sequence; D001549:Benzamides; D017931:DNA Primers; D016903:Drug Monitoring; D005500:Follow-Up Studies; D016044:Fusion Proteins, bcr-abl / Q000235:genetics*; D006801:Humans; D000068877:Imatinib Mesylate; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy* / Q000235:genetics*; D009154:Mutation; D010879:Piperazines / Q000627:therapeutic use*; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length; D011743:Pyrimidines / Q000627:therapeutic use*; D012333:RNA, Messenger / Q000235:genetics*; D012189:Retrospective Studies
D001549:Benzamides; D017931:DNA Primers; D010879:Piperazines; D011743:Pyrimidines; D012333:RNA, Messenger; D000068877:Imatinib Mesylate; D016044:Fusion Proteins, bcr-abl