Tyrosine kinase inhibitor STI571 (Imatinib) cooperates with wild-type p53 on K562 cell line to enhance its proapoptotic effects

Acta Haematol. 2005;114(3):150-4. doi: 10.1159/000087889.


In order to ascertain whether p53 has a role in chronic myeloid leukemia hematopoietic progenitor response to the innovative tyrosine kinase inhibitor STI571 (Imatinib), we overexpressed a wild type (wt) p53 construct in the K562 cell line, generated from a human blast crisis and lacking endogenous p53. Wt p53 overexpression was associated with a significant reduction of bcr-abl expression levels resulting, at least in part, from post-transcriptional events affecting the stability of p210 bcr-abl fusion protein. Moreover, we demonstrated that p53 overexpression enhances the commitment to the apoptotic death fate of K562 following its in vitro exposure to 1 microM STI571. Multiple mechanisms are involved in p53 impact on K562 survival: Most importantly, we found that a greater reduction of bcr-abl transcription by STI571 was associated with the overexpression of wt p53. Further studies are required to elucidate the mechanisms involved in the transcriptional repression of bcr-abl by STI571 and p53 and in their synergic effects on the clonal hematopoiesis of chronic myeloid leukemia.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis / drug effects*
  • Apoptosis / physiology*
  • Benzamides
  • Gene Expression
  • Genes, abl
  • Genes, p53
  • Humans
  • Imatinib Mesylate
  • K562 Cells
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / drug therapy
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / genetics
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / pathology
  • Neoplastic Stem Cells / drug effects
  • Neoplastic Stem Cells / pathology
  • Piperazines / pharmacology*
  • Protein Kinase Inhibitors / pharmacology*
  • Protein-Tyrosine Kinases / antagonists & inhibitors*
  • Pyrimidines / pharmacology*
  • Tumor Suppressor Protein p53 / genetics
  • Tumor Suppressor Protein p53 / physiology*


  • Benzamides
  • Piperazines
  • Protein Kinase Inhibitors
  • Pyrimidines
  • Tumor Suppressor Protein p53
  • Imatinib Mesylate
  • Protein-Tyrosine Kinases