Imatinib mesylate (STI571) prevents the mutator phenotype of Bcr-Abl in hematopoietic cell lines.
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.
van der Kuip
Heiko
H
Dr. Margarete Fischer-Bosch Institute of Clinical Pharmacology, Auerbachstr. 110, Stuttgart, Germany.
Moehring
Alexandra
A
Wohlbold
Lara
L
Miething
Cornelius
C
Duyster
Justus
J
Aulitzky
Walter E
WE
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*
D000970:Antineoplastic Agents; D001549:Benzamides; D010879:Piperazines; D011743:Pyrimidines; D000068877:Imatinib Mesylate; D007041:Hypoxanthine Phosphoribosyltransferase; D016044:Fusion Proteins, bcr-abl