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.
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.
authors.affiliation: Department of Hematology, Atomic Bomb Disease and Hibakusha Medicine Unit, Atomic Bomb Disease Institute, Nagasaki University, Nagasaki City, Nagasaki, Japan; Nagasaki CML Study Group, Nagasaki, Japan.
authors.forename: Hidehiro
authors.initials: H
authors.lastname: Itonaga
authors.affiliation: Nagasaki CML Study Group, Nagasaki, Japan. Electronic address: tsushima@hospital.sasebo.nagasaki.jp.
authors.forename: Hideki
authors.initials: H
authors.lastname: Tsushima
authors.affiliation: Department of Hematology, Atomic Bomb Disease and Hibakusha Medicine Unit, Atomic Bomb Disease Institute, Nagasaki University, Nagasaki City, Nagasaki, Japan; Nagasaki CML Study Group, Nagasaki, Japan.
authors.forename: Daisuke
authors.initials: D
authors.lastname: Imanishi
authors.affiliation: Department of Hematology, Atomic Bomb Disease and Hibakusha Medicine Unit, Atomic Bomb Disease Institute, Nagasaki University, Nagasaki City, Nagasaki, Japan; Nagasaki CML Study Group, Nagasaki, Japan.
authors.forename: Tomoko
authors.initials: T
authors.lastname: Hata
authors.affiliation: Department of Laboratory Medicine, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki City, Nagasaki, Japan.
authors.forename: Yuko
authors.initials: Y
authors.lastname: Doi
authors.affiliation: Department of Laboratory Medicine, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki City, Nagasaki, Japan.
authors.forename: Sayaka
authors.initials: S
authors.lastname: Mori
authors.affiliation: Department of Laboratory Medicine, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki City, Nagasaki, Japan.
authors.forename: Daisuke
authors.initials: D
authors.lastname: Sasaki
authors.affiliation: Department of Laboratory Medicine, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki City, Nagasaki, Japan.
authors.forename: Hiroo
authors.initials: H
authors.lastname: Hasegawa
authors.affiliation: Nagasaki CML Study Group, Nagasaki, Japan.
authors.forename: Emi
authors.initials: E
authors.lastname: Matsuo
authors.affiliation: Nagasaki CML Study Group, Nagasaki, Japan.
authors.forename: Jun
authors.initials: J
authors.lastname: Nakashima
authors.affiliation: Department of Hematology, Atomic Bomb Disease and Hibakusha Medicine Unit, Atomic Bomb Disease Institute, Nagasaki University, Nagasaki City, Nagasaki, Japan; Nagasaki CML Study Group, Nagasaki, Japan.
authors.forename: Takeharu
authors.initials: T
authors.lastname: Kato
authors.affiliation: Department of Hematology, Atomic Bomb Disease and Hibakusha Medicine Unit, Atomic Bomb Disease Institute, Nagasaki University, Nagasaki City, Nagasaki, Japan; Nagasaki CML Study Group, Nagasaki, Japan.
authors.forename: Makiko
authors.initials: M
authors.lastname: Horai
authors.affiliation: Department of Hematology, Atomic Bomb Disease and Hibakusha Medicine Unit, Atomic Bomb Disease Institute, Nagasaki University, Nagasaki City, Nagasaki, Japan; Nagasaki CML Study Group, Nagasaki, Japan.
authors.forename: Masataka
authors.initials: M
authors.lastname: Taguchi
authors.affiliation: Department of Hematology, Atomic Bomb Disease and Hibakusha Medicine Unit, Atomic Bomb Disease Institute, Nagasaki University, Nagasaki City, Nagasaki, Japan; Nagasaki CML Study Group, Nagasaki, Japan.
authors.forename: Masatoshi
authors.initials: M
authors.lastname: Matsuo
authors.affiliation: Department of Hematology, Atomic Bomb Disease and Hibakusha Medicine Unit, Atomic Bomb Disease Institute, Nagasaki University, Nagasaki City, Nagasaki, Japan; Nagasaki CML Study Group, Nagasaki, Japan.
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Taniguchi
authors.affiliation: Nagasaki CML Study Group, Nagasaki, Japan.
authors.forename: Junnya
authors.initials: J
authors.lastname: Makiyama
authors.affiliation: Nagasaki CML Study Group, Nagasaki, Japan.
authors.forename: Shinya
authors.initials: S
authors.lastname: Sato
authors.affiliation: Nagasaki CML Study Group, Nagasaki, Japan.
authors.forename: Kensuke
authors.initials: K
authors.lastname: Horio
authors.affiliation: Department of Hematology, Atomic Bomb Disease and Hibakusha Medicine Unit, Atomic Bomb Disease Institute, Nagasaki University, Nagasaki City, Nagasaki, Japan; Nagasaki CML Study Group, Nagasaki, Japan.
authors.forename: Koji
authors.initials: K
authors.lastname: Ando
authors.affiliation: Nagasaki CML Study Group, Nagasaki, Japan.
authors.forename: Yuji
authors.initials: Y
authors.lastname: Moriwaki
authors.affiliation: Department of Hematology, Atomic Bomb Disease and Hibakusha Medicine Unit, Atomic Bomb Disease Institute, Nagasaki University, Nagasaki City, Nagasaki, Japan; Nagasaki CML Study Group, Nagasaki, Japan.
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Sawayama
authors.affiliation: Nagasaki CML Study Group, Nagasaki, Japan.
authors.forename: Daisuke
authors.initials: D
authors.lastname: Ogawa
authors.affiliation: Nagasaki CML Study Group, Nagasaki, Japan.
authors.forename: Reishi
authors.initials: R
authors.lastname: Yamasaki
authors.affiliation: Nagasaki CML Study Group, Nagasaki, Japan.
authors.forename: Yumi
authors.initials: Y
authors.lastname: Takasaki
authors.affiliation: Department of Hematology, Atomic Bomb Disease and Hibakusha Medicine Unit, Atomic Bomb Disease Institute, Nagasaki University, Nagasaki City, Nagasaki, Japan; Nagasaki CML Study Group, Nagasaki, Japan.
authors.forename: Yoshitaka
authors.initials: Y
authors.lastname: Imaizumi
authors.affiliation: Department of Hematology, Atomic Bomb Disease and Hibakusha Medicine Unit, Atomic Bomb Disease Institute, Nagasaki University, Nagasaki City, Nagasaki, Japan; Nagasaki CML Study Group, Nagasaki, Japan.
authors.forename: Jun
authors.initials: J
authors.lastname: Taguchi
authors.affiliation: Nagasaki CML Study Group, Nagasaki, Japan.
authors.forename: Yasuhisa
authors.initials: Y
authors.lastname: Kawaguchi
authors.affiliation: Nagasaki CML Study Group, Nagasaki, Japan.
authors.forename: Shinichiro
authors.initials: S
authors.lastname: Yoshida
authors.affiliation: Nagasaki CML Study Group, Nagasaki, Japan.
authors.forename: Tatsuro
authors.initials: T
authors.lastname: Joh
authors.affiliation: Nagasaki CML Study Group, Nagasaki, Japan.
authors.forename: Yukiyoshi
authors.initials: Y
authors.lastname: Moriuchi
authors.affiliation: Nagasaki CML Study Group, Nagasaki, Japan.
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Nonaka
authors.affiliation: Nagasaki CML Study Group, Nagasaki, Japan.
authors.forename: Hisashi
authors.initials: H
authors.lastname: Soda
authors.affiliation: Laboratory of Hematoimmunology, Department of Clinical Laboratory Sciences, School of Health Sciences, Faculty of Medicine, University of the Ryukyus, Nishihara, Okinawa, Japan.
authors.forename: Takuya
authors.initials: T
authors.lastname: Fukushima
authors.affiliation: Transfusion and Cell Therapy Unit, Nagasaki University Hospital, Nagasaki, Japan.
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Nagai
authors.affiliation: Nagasaki CML Study Group, Nagasaki, Japan.
authors.forename: Shimeru
authors.initials: S
authors.lastname: Kamihira
authors.affiliation: Nagasaki CML Study Group, Nagasaki, Japan.
authors.forename: Masao
authors.initials: M
authors.lastname: Tomonaga
authors.affiliation: Department of Laboratory Medicine, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki City, Nagasaki, Japan.
authors.forename: Katsunori
authors.initials: K
authors.lastname: Yanagihara
authors.affiliation: Department of Hematology, Atomic Bomb Disease and Hibakusha Medicine Unit, Atomic Bomb Disease Institute, Nagasaki University, Nagasaki City, Nagasaki, Japan; Nagasaki CML Study Group, Nagasaki, Japan.
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Miyazaki
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000704:Analysis of Variance; D001549:Benzamides / Q000009:adverse effects / Q000627:therapeutic use; D004252:DNA Mutational Analysis; D004305:Dose-Response Relationship, Drug; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D005260:Female; D016044:Fusion Proteins, bcr-abl / Q000235:genetics*; D015973:Gene Expression Regulation, Leukemic; D006801:Humans; D000068877:Imatinib Mesylate; D007564:Japan; D015466:Leukemia, Myeloid, Chronic-Phase / Q000175:diagnosis / Q000188:drug therapy* / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010879:Piperazines / Q000009:adverse effects / Q000627:therapeutic use; D011446:Prospective Studies; D047428:Protein Kinase Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D011743:Pyrimidines / Q000009:adverse effects / Q000627:therapeutic use; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012307:Risk Factors; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: C581634:BCR-ABL1 fusion protein, human; D001549:Benzamides; D010879:Piperazines; D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; D000068877:Imatinib Mesylate; D016044:Fusion Proteins, bcr-abl
keywords: Alternative splicing; BCR-ABL1; Chronic myelogenous leukemia; Mutation; Resistance