The chemokine interleukin-8 and the surface activation protein CD69 are markers for Bcr-Abl activity in chronic myeloid leukemia

Mol Oncol. 2008 Oct;2(3):272-81. doi: 10.1016/j.molonc.2008.07.003. Epub 2008 Jul 23.

Abstract

We have identified differentially regulated genes in chronic myeloid leukemia (CML) cells upon short treatment with the broad-spectrum Bcr-Abl inhibitor dasatinib. The highly specific Bcr-Abl inhibitor nilotinib caused a very similar gene expression signature, validating the identified differentially regulated genes as a read-out of Bcr-Abl activity and implying that Bcr-Abl is the functionally central target of dasatinib in CML cells. Among the strongest downregulated genes, we have further validated the activation marker CD69 and the chemokine interleukin (IL)-8. Expression of both proteins is upregulated upon Bcr-Abl expression and inhibited by dasatinib and nilotinib. IL-8 may thus be a useful marker for the monitoring of CML inhibitor efficacy and play a potential pathophysiological role in CML.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antigens, CD / analysis*
  • Antigens, CD / genetics
  • Antigens, Differentiation, T-Lymphocyte / analysis*
  • Antigens, Differentiation, T-Lymphocyte / genetics
  • Biomarkers / analysis
  • Dasatinib
  • Down-Regulation / drug effects
  • Drug Monitoring / methods*
  • Fusion Proteins, bcr-abl / metabolism*
  • Gene Expression Regulation, Neoplastic / drug effects
  • Interleukin-8 / analysis*
  • Interleukin-8 / genetics
  • Lectins, C-Type
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / diagnosis*
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / drug therapy
  • Pyrimidines / pharmacology
  • Thiazoles / pharmacology

Substances

  • 4-methyl-N-(3-(4-methylimidazol-1-yl)-5-(trifluoromethyl)phenyl)-3-((4-pyridin-3-ylpyrimidin-2-yl)amino)benzamide
  • Antigens, CD
  • Antigens, Differentiation, T-Lymphocyte
  • Biomarkers
  • CD69 antigen
  • Interleukin-8
  • Lectins, C-Type
  • Pyrimidines
  • Thiazoles
  • Fusion Proteins, bcr-abl
  • Dasatinib