title: 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.
  
  
  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.
  
  
  CONCLUSIONS
  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.affiliation: Temple University School of Medicine, Department of Neuroscience, 3500 N. Broad St., Medical Education and Research Bld, Rm 746, Philadelphia, PA 19140-5104, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Kogan
authors.forename: Tracy
authors.initials: T
authors.lastname: Fischer-Smith
authors.forename: Rafal
authors.initials: R
authors.lastname: Kaminsky
authors.forename: Gabrielle
authors.initials: G
authors.lastname: Lehmicke
authors.forename: Jay
authors.initials: J
authors.lastname: Rappaport
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use*; D045744:Cell Line, Tumor; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy* / Q000201:enzymology / Q000378:metabolism / Q000473:pathology; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors*; D016186:Receptor, Macrophage Colony-Stimulating Factor / Q000378:metabolism*; D015398:Signal Transduction; D015854:Up-Regulation
chemical_list: D000970:Antineoplastic Agents; D011505:Protein-Tyrosine Kinases; D016186:Receptor, Macrophage Colony-Stimulating Factor