title: Successful treatment with nilotinib after imatinib failure in a CML patient with a four-way Ph chromosome translocation and point mutations in BCR/ABL gene.
abstract: Chronic myelogenous leukemia (CML) is characterized by Philadelphia (Ph) chromosome with a chimeric gene BCR-ABL created by reciprocal t(9:22) (q34;q11) translocation. Variant Ph chromosome translocations involving chromosomes other than 9 and 22 are found in 5-10% of CML cases. We here report a CML patient who carries a four-way Ph chromosome translocation, t(9;22;15;19) (q34;q11;q15;q13). The patient was diagnosed in 1997 and initially treated with hydroxyurea. In 2002, treatment with imatinib, a selective BCR-ABL tyrosine kinase inhibitor (TKI), was started but Ph-positive chromosomes remained at the levels of 42-65%, indicating imatinib failure. In 2006, the point mutations of F359I and L387M were detected in BCR/ABL gene, which may be related to imatinib failure. Treatment with nilotinib, a TKI with high target specificity, was then started which resulted in durable major molecular response. Administration of nilotinib offered an effective treatment in a CML patient with variant Ph chromosome translocations and BCR-ABL point mutations after imatinib failure.
authors.affiliation: Division of Hematology, Department of Internal Medicine, Hyogo College of Medicine, 1-1 Mukogawa-cho, Nishinomiya, Hyogo, 663-8501, Japan.
authors.forename: Masaya
authors.initials: M
authors.lastname: Okada
authors.affiliation: Division of Hematology, Department of Internal Medicine, Hyogo College of Medicine, 1-1 Mukogawa-cho, Nishinomiya, Hyogo, 663-8501, Japan.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Satake
authors.affiliation: Division of Hematology, Department of Internal Medicine, Hyogo College of Medicine, 1-1 Mukogawa-cho, Nishinomiya, Hyogo, 663-8501, Japan.
authors.forename: Katsuji
authors.initials: K
authors.lastname: Kaida
authors.affiliation: Division of Hematology, Department of Internal Medicine, Hyogo College of Medicine, 1-1 Mukogawa-cho, Nishinomiya, Hyogo, 663-8501, Japan.
authors.forename: Kyoko
authors.initials: K
authors.lastname: Taniguchi
authors.affiliation: Division of Hematology, Department of Internal Medicine, Hyogo College of Medicine, 1-1 Mukogawa-cho, Nishinomiya, Hyogo, 663-8501, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Yoshihara
authors.affiliation: Division of Hematology, Department of Internal Medicine, Hyogo College of Medicine, 1-1 Mukogawa-cho, Nishinomiya, Hyogo, 663-8501, Japan.
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Ikegame
authors.affiliation: Division of Hematology, Department of Internal Medicine, Hyogo College of Medicine, 1-1 Mukogawa-cho, Nishinomiya, Hyogo, 663-8501, Japan.|Laboratory of Cell Transplantation, Institute for Advanced Medical Sciences, Hyogo College of Medicine, 1-1 Mukogawa-cho, Nishinomiya, Hyogo, 663-8501, Japan.
authors.forename: Hiroya
authors.initials: H
authors.lastname: Tamaki
authors.affiliation: Division of Hematology, Department of Internal Medicine, Hyogo College of Medicine, 1-1 Mukogawa-cho, Nishinomiya, Hyogo, 663-8501, Japan.
authors.forename: Toshihiro
authors.initials: T
authors.lastname: Soma
authors.affiliation: Laboratory of Cell Transplantation, Institute for Advanced Medical Sciences, Hyogo College of Medicine, 1-1 Mukogawa-cho, Nishinomiya, Hyogo, 663-8501, Japan. fuji-y@hyo-med.ac.jp.
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Fujimori
authors.affiliation: Division of Hematology, Department of Internal Medicine, Hyogo College of Medicine, 1-1 Mukogawa-cho, Nishinomiya, Hyogo, 663-8501, Japan.|Laboratory of Cell Transplantation, Institute for Advanced Medical Sciences, Hyogo College of Medicine, 1-1 Mukogawa-cho, Nishinomiya, Hyogo, 663-8501, Japan.
authors.forename: Hiroyasu
authors.initials: H
authors.lastname: Ogawa
mesh_terms: D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use; D001549:Benzamides; D019008:Drug Resistance, Neoplasm; D005260:Female; D016044:Fusion Proteins, bcr-abl / Q000037:antagonists & inhibitors / Q000235:genetics*; D006801:Humans; D000068877:Imatinib Mesylate; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy* / Q000235:genetics*; D010677:Philadelphia Chromosome; D010879:Piperazines / Q000627:therapeutic use; D017354:Point Mutation; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors / Q000235:genetics*; D011743:Pyrimidines / Q000627:therapeutic use*; D014178:Translocation, Genetic; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D001549:Benzamides; D010879:Piperazines; D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; D000068877:Imatinib Mesylate; D011505:Protein-Tyrosine Kinases; D016044:Fusion Proteins, bcr-abl; C498826:nilotinib