Effects of a Selective Inhibitor of the Abl Tyrosine Kinase on the Growth of Bcr-Abl Positive Cells

Nat Med. 1996 May;2(5):561-6. doi: 10.1038/nm0596-561.

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Benzamides
  • Blood Cells / drug effects
  • Bone Marrow / drug effects
  • Dose-Response Relationship, Drug
  • Enzyme Inhibitors / pharmacology*
  • Evaluation Studies as Topic
  • Fusion Proteins, bcr-abl*
  • Humans
  • Imatinib Mesylate
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / drug therapy*
  • Mice
  • Piperazines / pharmacology*
  • Protein-Tyrosine Kinases / antagonists & inhibitors*
  • Proto-Oncogene Proteins c-abl / antagonists & inhibitors*
  • Pyrimidines / pharmacology*
  • Stem Cells / drug effects
  • Tumor Cells, Cultured

Substances

  • Benzamides
  • Enzyme Inhibitors
  • Piperazines
  • Pyrimidines
  • Imatinib Mesylate
  • Protein-Tyrosine Kinases
  • Fusion Proteins, bcr-abl
  • Proto-Oncogene Proteins c-abl