Effects of a selective inhibitor of the Abl tyrosine kinase on the growth of Bcr-Abl positive cells.
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.
Druker
B J
BJ
Division of Hematology and Medical Oncology, Oregon Health Sciences University, Portland, USA.
Tamura
S
S
Buchdunger
E
E
Ohno
S
S
Segal
G M
GM
Fanning
S
S
Zimmermann
J
J
Lydon
N B
NB
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
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