CSF-1R up-regulation is associated with response to pharmacotherapy targeting tyrosine kinase activity in AML cell lines

Anticancer Res. 2012 Mar;32(3):893-9.

Abstract

Background: The oncogenic potential of colony stimulating factor 1 receptor (CSF-1R) has been well described, while its relevance for human acute myelogenous leukemia (AML) is still undetermined. In a recent clinical trial for AML, sunitinib was found to hold potential therapeutic benefit, however, the mechanism for this remains unknown.

Materials and methods: In this study, we treated three myeloid cell lines, Mono-Mac 1, THP-1, and U937, with sunitinib, and a small-molecule CSF-1R inhibitor (cFMS-I) to test the anticancer effect of such treatment.

Results: Mono-Mac 1 cells had inhibited proliferation and extracellular-signal regulated kinase activity as a result of CSF-1R inhibition and a dose-dependent increase in CSF-1R expression with both sunitinib and cFMS-I.

Conclusion: Our results suggest potential for CSF-1R as an important target of sunitinib or other similar drugs. Future study of CSF-1R may produce more targeted therapeutic approaches and aid in the development of personalized medicine for AML.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Antineoplastic Agents / therapeutic use*
  • Cell Line, Tumor
  • Humans
  • Leukemia, Myeloid, Acute / drug therapy*
  • Leukemia, Myeloid, Acute / enzymology
  • Leukemia, Myeloid, Acute / metabolism
  • Leukemia, Myeloid, Acute / pathology
  • Protein-Tyrosine Kinases / antagonists & inhibitors*
  • Receptor, Macrophage Colony-Stimulating Factor / metabolism*
  • Signal Transduction
  • Up-Regulation*

Substances

  • Antineoplastic Agents
  • Protein-Tyrosine Kinases
  • Receptor, Macrophage Colony-Stimulating Factor