title: In vitro drug resistance to imatinib and mutation of ABL gene in childhood Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia.
abstract: Imatinib, the ABL kinase inhibitor, is used not only for Philadelphia chromosome-positive (Ph + ) chronic myelogenous leukemia, but also for Ph + acute lymphoblastic leukemia (ALL), although resistance to the drug tends to develop in an early stage of the clinical course. We describe a childhood refractory Ph + ALL patient in whom progressive resistance to imatinib was correlated with the appearance of a mutation in the BCR-ABL kinase domain and in vitro drug resistance to imatinib as determined by the methyl-thiazol-tetrazolium (MTT) assay. A missense mutation of T to C (Y253H) of the ABL gene was identified in the resistant clone, suggesting that this mutation may play an etiological role in the rapid loss of drug sensitivity.
authors.affiliation: Department of Pediatrics, Graduate School of Medicine, University of Tokyo, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Kawaguchi
authors.forename: Takeshi
authors.initials: T
authors.lastname: Taketani
authors.forename: Teruaki
authors.initials: T
authors.lastname: Hongo
authors.forename: Myoung-Ja
authors.initials: MJ
authors.lastname: Park
authors.forename: Katsuyoshi
authors.initials: K
authors.lastname: Koh
authors.forename: Kohmei
authors.initials: K
authors.lastname: Ida
authors.forename: Miyuki
authors.initials: M
authors.lastname: Kobayashi
authors.forename: Junko
authors.initials: J
authors.lastname: Takita
authors.forename: Tomohiko
authors.initials: T
authors.lastname: Taki
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Yoshino
authors.forename: Fumio
authors.initials: F
authors.lastname: Bessho
authors.forename: Yasuhide
authors.initials: Y
authors.lastname: Hayashi
mesh_terms: D001549:Benzamides; D002470:Cell Survival / Q000187:drug effects; D002648:Child; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D016313:Genes, abl / Q000235:genetics* / Q000502:physiology; D006801:Humans; D000068877:Imatinib Mesylate; D008297:Male; D020125:Mutation, Missense; D010677:Philadelphia Chromosome; D010879:Piperazines / Q000494:pharmacology / Q000627:therapeutic use*; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000175:diagnosis / Q000188:drug therapy* / Q000235:genetics; D011743:Pyrimidines / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: D001549:Benzamides; D010879:Piperazines; D011743:Pyrimidines; D000068877:Imatinib Mesylate