Abstract
We recently developed an Invader assay combined with reverse transcriptase polymerase-chain-reaction in order to quantify T315I bcr-abl transcripts. Using this assay, we serially monitored T315I bcr-abl transcripts in chronic myeloid leukemia (CML) patients whose bcr-abl transcripts were still detectable at 6 months after starting imatinib therapy. Although, we continued to monitor bcr-abl transcripts in 14 CML patients (13 chronic phases and 1 accelerated phase) for up to 12 months, there were no patients who were apparently resistant to imatinib due to the T315I mutation. In contrast, in a case of Philadelphia chromosome-positive acute lymphoid leukemia being treated with chemotherapy including imatinib, we monitored both wild-type and T315I bcr-abl transcripts, and found increased levels of T315I transcripts during relapse (0% at the time of diagnosis and 54.8% at relapse). Thus, our new approach could be a useful tool to study the kinetics of mutant clones and the pharmacokinetics of drug resistance with regard to the T315I mutation.
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Acknowledgments
This study was supported in part by a grant for clinical cancer research from the Ministry of Health, Labour and Welfare of Japan. We would like to thank the nursing staff of Tokyo Metropolitan Cancer and Infectious Diseases Center, Komagome Hospital for their assistance in the collection of samples from the patients included in this study. We would also like to thank the staff of the Hematology Division, Tokyo Metropolitan Cancer and Infectious Diseases Center, Komagome Hospital, for their excellent patient care.
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M. Yamamoto and K. Kakihana contributed equally to this study.
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Yamamoto, M., Kakihana, K., Ohashi, K. et al. Serial monitoring of T315I BCR-ABL mutation by Invader assay combined with RT-PCR. Int J Hematol 89, 482–488 (2009). https://doi.org/10.1007/s12185-009-0290-9
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DOI: https://doi.org/10.1007/s12185-009-0290-9