title: Effects of a selective inhibitor of the Abl tyrosine kinase on the growth of Bcr-Abl positive cells.
abstract: The bcr-abl oncogene, present in 95% of patients with chronic myelogenous leukemia (CML), has been implicated as the cause of this disease. A compound, designed to inhibit the Abl protein tyrosine kinase, was evaluated for its effects on cells containing the Bcr-Abl fusion protein. Cellular proliferation and tumor formation by Bcr-Abl-expressing cells were specifically inhibited by this compound. In colony-forming assays of peripheral blood or bone marrow from patients with CML, there was a 92-98% decrease in the number of bcr-abl colonies formed but no inhibition of normal colony formation. This compound may be useful in the treatment of bcr-abl-positive leukemias.
authors.affiliation: Division of Hematology and Medical Oncology, Oregon Health Sciences University, Portland, USA.
authors.forename: B J
authors.initials: BJ
authors.lastname: Druker
authors.forename: S
authors.initials: S
authors.lastname: Tamura
authors.forename: E
authors.initials: E
authors.lastname: Buchdunger
authors.forename: S
authors.initials: S
authors.lastname: Ohno
authors.forename: G M
authors.initials: GM
authors.lastname: Segal
authors.forename: S
authors.initials: S
authors.lastname: Fanning
authors.forename: J
authors.initials: J
authors.lastname: Zimmermann
authors.forename: N B
authors.initials: NB
authors.lastname: Lydon
mesh_terms: D000818:Animals; D001549:Benzamides; D001773:Blood Cells / Q000187:drug effects; D001853:Bone Marrow / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005069:Evaluation Studies as Topic; D016044:Fusion Proteins, bcr-abl; D006801:Humans; D000068877:Imatinib Mesylate; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy*; D051379:Mice; D010879:Piperazines / Q000494:pharmacology*; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors*; D016315:Proto-Oncogene Proteins c-abl / Q000037:antagonists & inhibitors*; D011743:Pyrimidines / Q000494:pharmacology*; D013234:Stem Cells / Q000187:drug effects; D014407:Tumor Cells, Cultured
chemical_list: D001549:Benzamides; D004791:Enzyme Inhibitors; D010879:Piperazines; D011743:Pyrimidines; D000068877:Imatinib Mesylate; D011505:Protein-Tyrosine Kinases; D016044:Fusion Proteins, bcr-abl; D016315:Proto-Oncogene Proteins c-abl