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

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.

• Authors: Michael Kogan, Tracy Fischer-Smith, Rafal Kaminsky, Gabrielle Lehmicke, Jay Rappaport
• Journal: Anticancer research (Anticancer Res) Vol. 32 Issue 3 Pg. 893-9 (Mar 2012) ISSN: 1791-7530 [Electronic] Greece
• PMID: 22399609 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)

Chemical References

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

Topics

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