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.