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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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Title: 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
Authors: Itonaga, Hidehiro / Tsushima, Hideki / Imanishi, Daisuke / Hata, Tomoko / Doi, Yuko / Mori, Sayaka / Sasaki, Daisuke / Hasegawa, Hiroo / Matsuo, Emi / Nakashima, Jun / Kato, Takeharu / Horai, Makiko / Taguchi, Masataka / Matsuo, Masatoshi / Taniguchi, Hiroaki / Makiyama, Junnya / Sato, Shinya / Horio, Kensuke / Ando, Koji / Moriwaki, Yuji / Sawayama, Yasushi / Ogawa, Daisuke / Yamasaki, Reishi / Takasaki, Yumi / Imaizumi, Yoshitaka / Taguchi, Jun / Kawaguchi, Yasuhisa / Yoshida, Shinichiro / Joh, Tatsuro / Moriuchi, Yukiyoshi / Nonaka, Hiroaki / Soda, Hisashi / Fukushima, Takuya / Nagai, Kazuhiro / Kamihira, Shimeru / Tomonaga, Masao / Yanagihara, Katsunori / Miyazaki, Yasushi
Issue Date: Jan-2014
Publisher: Elsevier Limited
Citation: Leukemia Research, 38(1), pp.76-83; 2014
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: Alternative splicing / BCR-ABL1 / Chronic myelogenous leukemia / Mutation / Resistance
URI: http://hdl.handle.net/10069/34111
ISSN: 01452126
DOI: 10.1016/j.leukres.2013.10.022
Rights: © 2013 Elsevier Ltd. / NOTICE: this is the author’s version of a work that was accepted for publication in Leukemia Research. Changes resulting from the publishing process, such as peer review, editing, corrections, structural formatting, and other quality control mechanisms may not be reflected in this document. Changes may have been made to this work since it was submitted for publication. A definitive version was subsequently published in Leukemia Research, 38, ISS1, (2014)
Type: Journal Article
Text Version: author
Appears in Collections:Articles in academic journal

Citable URI : http://hdl.handle.net/10069/34111

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