title: Imatinib mesylate (STI571) prevents the mutator phenotype of Bcr-Abl in hematopoietic cell lines.
abstract: Progression of CML from chronic phase to blast crisis is accompanied by accumulating genetic alterations. To analyze whether this abnormality can be prevented by inhibition of Bcr-Abl, we measured the frequency of spontaneous and irradiation-induced HPRT mutations in cells treated with or without imatinib mesylate (Gleevec, STI571). Imatinib treatment of cells expressing Bcr-Abl reversed the mutation frequency to a value comparable to that of Bcr-Abl negative cells. Experiments with a Bcr-Abl deletion mutant indicate that in addition to the kinase activity, protein-protein interactions are required for induction of the mutator phenotype by Bcr-Abl.
authors.affiliation: Dr. Margarete Fischer-Bosch Institute of Clinical Pharmacology, Auerbachstr. 110, Stuttgart, Germany.
authors.forename: Heiko
authors.initials: H
authors.lastname: van der Kuip
authors.forename: Alexandra
authors.initials: A
authors.lastname: Moehring
authors.forename: Lara
authors.initials: L
authors.lastname: Wohlbold
authors.forename: Cornelius
authors.initials: C
authors.lastname: Miething
authors.forename: Justus
authors.initials: J
authors.lastname: Duyster
authors.forename: Walter E
authors.initials: WE
authors.lastname: Aulitzky
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D001549:Benzamides; D002460:Cell Line; D016044:Fusion Proteins, bcr-abl / Q000235:genetics*; D006413:Hematopoietic System / Q000166:cytology / Q000187:drug effects; D006801:Humans; D007041:Hypoxanthine Phosphoribosyltransferase / Q000235:genetics; D000068877:Imatinib Mesylate; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy / Q000235:genetics*; D009154:Mutation; D010641:Phenotype; D010879:Piperazines / Q000494:pharmacology*; D011743:Pyrimidines / Q000494:pharmacology*
chemical_list: D000970:Antineoplastic Agents; D001549:Benzamides; D010879:Piperazines; D011743:Pyrimidines; D000068877:Imatinib Mesylate; D007041:Hypoxanthine Phosphoribosyltransferase; D016044:Fusion Proteins, bcr-abl