Differential tyrosine phosphorylation of leukemic cells during apoptosis as a result of treatment with imatinib mesylate

Biochem Biophys Res Commun. 2005 Oct 28;336(3):942-51. doi: 10.1016/j.bbrc.2005.08.201.


Bcr-Abl fusion tyrosine kinase contributes to leukemic transformation. Imatinib mesylate inhibits Bcr-Abl tyrosine kinase, resulting in a blockage of tyrosine phosphorylation in its downstream pathways. We analyzed the alteration of tyrosine phosphorylation, on BCR/ABL+ chronic myelogenous leukemia cells, after treatment with imatinib mesylate. Data were collected using a two-dimensional gel electrophoresis followed by Western blot and mass spectrometry. The inhibition of Bcr-Abl tyrosine kinase by 2.5 microM imatinib mesylate caused both cell cycle arrest in the G0/G1 phase and increased the portion of apoptotic cells. As a result, the population of leukemic cells decreased by 30% and 70% compared to controls at 24 and 72 h, respectively. Furthermore, treatment with imatinib mesylate altered tyrosine phosphorylation of 24 protein spots as the incubation time proceeded from 0 to 24 and 72 h. Ten of the 24 protein spots are visible at all three times. Four are detectable at both the 0 and 24 h points in time. Eight were detectable only at time 0.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / pharmacology*
  • Apoptosis*
  • Benzamides
  • Blotting, Western
  • Cell Cycle / drug effects
  • Cell Cycle Proteins / genetics
  • Cell Cycle Proteins / metabolism
  • Cell Proliferation / drug effects
  • Electrophoresis, Gel, Two-Dimensional
  • Fusion Proteins, bcr-abl / antagonists & inhibitors*
  • Humans
  • Imatinib Mesylate
  • K562 Cells
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / enzymology*
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / metabolism
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / pathology
  • Phosphorylation
  • Piperazines / pharmacology*
  • Protein Kinase Inhibitors / pharmacology*
  • Proteome / metabolism
  • Pyrimidines / pharmacology*
  • Transcription, Genetic / drug effects
  • Tyrosine / metabolism


  • Antineoplastic Agents
  • Benzamides
  • Cell Cycle Proteins
  • Piperazines
  • Protein Kinase Inhibitors
  • Proteome
  • Pyrimidines
  • abl-bcr fusion protein, human
  • Tyrosine
  • Imatinib Mesylate
  • Fusion Proteins, bcr-abl