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Molecular analysis of the BCR-ABL1 kinase domain in chronic-phase chronic myelogenous leukemia treated with tyrosine kinase inhibitors in practice: Study by the Nagasaki CML Study Group |
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| Authors: | Hidehiro Itonaga Hideki Tsushima Daisuke Imanishi Tomoko Hata Yuko Doi Sayaka Mori Daisuke Sasaki Hiroo Hasegawa Emi Matsuo Jun Nakashima Takeharu Kato Makiko Horai Masataka Taguchi Masatoshi Matsuo Hiroaki Taniguchi Junnya Makiyama Shinya Sato Kensuke Horio Koji Ando Yuji Moriwaki Yasushi Sawayama Daisuke Ogawa Reishi Yamasaki Yumi Takasaki Yoshitaka Imaizumi Jun Taguchi Yasuhisa Kawaguchi Shinichiro Yoshida Tatsuro Joh Yukiyoshi Moriuchi Hiroaki Nonaka Hisashi Soda Takuya Fukushima Kazuhiro Nagai Shimeru Kamihira Masao Tomonaga Katsunori Yanagihara Yasushi Miyazaki |
| Institution: | 1. Department of Hematology, Atomic Bomb Disease and Hibakusha Medicine Unit, Atomic Bomb Disease Institute, Nagasaki University, Nagasaki City, Nagasaki, Japan;2. Nagasaki CML Study Group, Nagasaki, Japan;3. Department of Laboratory Medicine, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki City, Nagasaki, Japan;4. Laboratory of Hematoimmunology, Department of Clinical Laboratory Sciences, School of Health Sciences, Faculty of Medicine, University of the Ryukyus, Nishihara, Okinawa, Japan;5. Transfusion and Cell Therapy Unit, Nagasaki University Hospital, Nagasaki, Japan |
| Abstract: | An appropriate trigger for BCR-ABL1 mutation analysis has not yet been established in unselected cohorts of chronic-phase chronic myelogenous leukemia patients. We examined 92 patients after 12 months of tyrosine kinase inhibitor (TKI) treatment in Nagasaki Prefecture, Japan. Univariate analysis revealed that significant factors associated with not attaining a major molecular response (MMR) were the presence of the minor BCR-ABL1 fusion gene, a low daily dose of TKI, and the emergence of BCR-ABL1 kinase domain mutations conferring resistance to imatinib. Factors associated with the loss of sustained MMR were a low daily dose of TKI and the emergence of alternatively spliced BCR-ABL1 mRNA with a 35-nucleotide insertion. Taken together, our results suggest that the search for BCR-ABL1 mutations should be initiated if patients have not achieved MMR following 12 months of TKI treatment. |
| Keywords: | Chronic myelogenous leukemia BCR-ABL1 Alternative splicing Mutation Resistance |
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