p21(Cip1) confers resistance to imatinib in human chronic myeloid leukemia cells

Cancer Lett. 2010 Jun 1;292(1):133-9. doi: 10.1016/j.canlet.2009.11.017. Epub 2009 Dec 29.

Abstract

Imatinib is a Bcr-Abl inhibitor used as first-line therapy of chronic myeloid leukemia (CML). p21(Cip1), initially described as a cell cycle inhibitor, also protects from apoptosis in some models. We describe that imatinib down-regulates p21(Cip1) expression in CML cells. Using K562 cells with inducible p21 expression and transient transfections we found that p21 confers partial resistance to imatinib-induced apoptosis. This protection is not related to the G2-arrest provoked by p21, a decrease in the imatinib activity against Bcr-Abl or a cytoplasmic localization of p21. The results suggest an involvement of p21(Cip1) in the response to imatinib in CML.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis / drug effects
  • Benzamides
  • Cell Line, Tumor
  • Cyclin-Dependent Kinase Inhibitor p21 / metabolism*
  • Drug Resistance, Neoplasm*
  • G2 Phase / drug effects
  • Humans
  • Imatinib Mesylate
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / drug therapy*
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / metabolism
  • Piperazines / antagonists & inhibitors*
  • Piperazines / therapeutic use*
  • Pyrimidines / antagonists & inhibitors*
  • Pyrimidines / therapeutic use*

Substances

  • Benzamides
  • CDKN1A protein, human
  • Cyclin-Dependent Kinase Inhibitor p21
  • Piperazines
  • Pyrimidines
  • Imatinib Mesylate