Dynamic change of T315I BCR-ABL kinase domain mutation in Korean chronic myeloid leukaemia patients during treatment with Abl tyrosine kinase inhibitors
Wan-Seok Kim
Molecular Genetic Research Institute, The Catholic University of Korea, Seoul, Korea
These authors contributed equally to this work.
Search for more papers by this authorDongho Kim
Molecular Genetic Research Institute, The Catholic University of Korea, Seoul, Korea
These authors contributed equally to this work.
Search for more papers by this authorCorresponding Author
Dong-Wook Kim
Molecular Genetic Research Institute, The Catholic University of Korea, Seoul, Korea
Division of Hematology, Seoul St. Mary's Hospital, The Catholic University of Korea, Seoul, Korea
Division of Hematology, Seoul St. Mary's Hospital, The Catholic University of Korea, 505 Banpo-dong, Seocho gu, Seoul, Korea.Search for more papers by this authorIl-Young Kweon
Division of Hematology, Seoul St. Mary's Hospital, The Catholic University of Korea, Seoul, Korea
Search for more papers by this authorSoo-Hyun Kim
Molecular Genetic Research Institute, The Catholic University of Korea, Seoul, Korea
Search for more papers by this authorHyun-Gyung Goh
Molecular Genetic Research Institute, The Catholic University of Korea, Seoul, Korea
Search for more papers by this authorSa-Hee Park
Division of Hematology, Seoul St. Mary's Hospital, The Catholic University of Korea, Seoul, Korea
Search for more papers by this authorJeong Lee
Molecular Genetic Research Institute, The Catholic University of Korea, Seoul, Korea
Search for more papers by this authorWan-Seok Kim
Molecular Genetic Research Institute, The Catholic University of Korea, Seoul, Korea
These authors contributed equally to this work.
Search for more papers by this authorDongho Kim
Molecular Genetic Research Institute, The Catholic University of Korea, Seoul, Korea
These authors contributed equally to this work.
Search for more papers by this authorCorresponding Author
Dong-Wook Kim
Molecular Genetic Research Institute, The Catholic University of Korea, Seoul, Korea
Division of Hematology, Seoul St. Mary's Hospital, The Catholic University of Korea, Seoul, Korea
Division of Hematology, Seoul St. Mary's Hospital, The Catholic University of Korea, 505 Banpo-dong, Seocho gu, Seoul, Korea.Search for more papers by this authorIl-Young Kweon
Division of Hematology, Seoul St. Mary's Hospital, The Catholic University of Korea, Seoul, Korea
Search for more papers by this authorSoo-Hyun Kim
Molecular Genetic Research Institute, The Catholic University of Korea, Seoul, Korea
Search for more papers by this authorHyun-Gyung Goh
Molecular Genetic Research Institute, The Catholic University of Korea, Seoul, Korea
Search for more papers by this authorSa-Hee Park
Division of Hematology, Seoul St. Mary's Hospital, The Catholic University of Korea, Seoul, Korea
Search for more papers by this authorJeong Lee
Molecular Genetic Research Institute, The Catholic University of Korea, Seoul, Korea
Search for more papers by this authorAbstract
We analysed the dynamic change of imatinib-resistant mutations in BCR-ABL kinase domain focusing on T315I mutation during dasatinib or nilotinib therapy. Fifty-five imatinib-resistant chronic myeloid leukaemia patients (32 patients with imatinib-resistant mutations and 23 patients without mutation) in different disease phases were treated with dasatinib (median 17.3 months) or nilotinib (median 6.8 months). Among the 32 patients with baseline mutation, mutations including M244V, G250E, E255K, M351T, H396R, S417Y, E450K and E459K disappeared in 8 patients and new mutations were detected in 9 patients, all of which were T315I. Among the 23 patients without baseline mutation, 4 patients showed newly developed mutations including T315I, T315I + E459K, M244V and F359V. The T315I was the most frequently detected mutation in imatinib therapy (16%, 9 of 55) as well as in dasatinib or nilotinib therapy (24%, 11 of 44). Patients with imatinib resistant baseline mutations had a higher rate of mutation development during dasatinib or nilotinib treatment compared to patients without baseline mutations (28% vs. 17%). Copyright © 2009 John Wiley & Sons, Ltd.
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