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FMS receptor for M-CSF (CSF-1) is sensitive to the kinase inhibitor imatinib and mutation of Asp-802 to Val confers resistance

Oncogene volume 25, pages 147–151 (2006)Cite this article

Abstract

The kinase inhibitor imatinib is used in the treatment of chronic myeloid leukaemia, where it targets the intracellular Bcr-Abl tyrosine kinase, and gastrointestinal stromal tumours, where it targets either the KIT or PDGF tyrosine kinase receptors. Here, we report that imatinib is also an effective inhibitor of the closely related FMS receptor for macrophage colony stimulating factor and that mutation of Asp 802 of FMS to Val confers imatinib resistance. Imatinib readily reverted the transformed phenotype of haemopoietic and fibroblast cell lines that express the oncogene v-fms and also inhibited the growth of the Bacl.2F5 macrophage cell line. The cellular IC50 value of imatinib for FMS was similar to those for Bcr-Abl and KIT. Consequently, imatinib may also prove effective for the treatment of diseases whose progression is dependent upon macrophage-colony stimulating factor, this includes certain aspects of cancer and inflammation.

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References

  • Aldskogius H . (2001). Expert Opin Ther Targets 5: 655–668.

  • Baker DA, Glover HR, Dibb NJ . (1994). Leukemia 8: 141–150.

  • Bohmer FD, Karagyozov L, Uecker A, Serve H, Botzki A, Mahboobi S et al. (2003). J Biol Chem 278: 5148–5155.

  • Buchdunger E, Cioffi CL, Law N, Stover D, Ohno-Jones S, Druker BJ et al. (2000). J Pharmacol Exp Ther 295: 139–145.

  • Buchdunger E, Zimmermann J, Mett H, Meyer T, Muller M, Druker BJ et al. (1996). Cancer Res 56: 100–104.

  • Caruana G, Ashman LK, Fujita J, Gonda TJ . (1993). Exp Hematol 21: 761–768.

  • Cohen P . (2002). Nat Rev Drug Discov 1: 309–315.

  • Corbin AS, La Rosee P, Stoffregen EP, Druker BJ, Deininger MW . (2003). Blood 101: 4611–4614.

  • Dewar AL, Cambareri AC, Zannettino AC, Miller BL, Doherty KV, Hughes TP et al. (2005). Blood 105: 3127–3132.

  • Dewar AL, Domaschenz RM, Doherty KV, Hughes TP, Lyons AB . (2003). Leukemia 17: 1713–1721.

  • Dibb NJ, Dilworth SM, Mol CD . (2004). Nat Rev Cancer 4: 718–727.

  • Dibb NJ, Green SM, Ralph P . (1990). Growth Factors 2: 301–311.

  • Druker BJ, Talpaz M, Resta DJ, Peng B, Buchdunger E, Ford JM et al. (2001). N Engl J Med 344: 1031–1037.

  • Frost MJ, Ferrao PT, Hughes TP, Ashman LK . (2002). Mol Cancer Ther 1: 1115–1124.

  • Glover HR, Baker DA, Celetti A, Dibb NJ . (1995). Oncogene 11: 1347–1356.

  • Joensuu H, Fletcher C, Dimitrijevic S, Silberman S, Roberts P, Demetri G . (2002). Lancet Oncol 3: 655–664.

  • Kacinski BM . (1997). Mol Reprod Dev 46: 71–74.

  • Krystal GW, Honsawek S, Litz J, Buchdunger E . (2000). Clin Cancer Res 6: 3319–3326.

  • Lin EY, Nguyen AV, Russell RG, Pollard JW . (2001). J Exp Med 193: 727–740.

  • Longley BJ, Reguera MJ, Ma Y . (2001). Leuk Res 25: 571–576.

  • Lynch TJ, Bell DW, Sordella R, Gurubhagavatula S, Okimoto RA, Brannigan BW et al. (2004). N Engl J Med 350: 2129–2139.

  • Ma Y, Zeng S, Metcalfe DD, Akin C, Dimitrijevic S, Butterfield JH et al. (2002). Blood 99: 1741–1744.

  • Mahon EX, Deininger MW, Schultheis B, Chabrol J, Reiffers J, Goldman JM et al. (2000). Blood 96: 1070–1079.

  • Mol CD, Dougan DR, Schneider TR, Skene RJ, Kraus ML, Scheibe DN et al. (2004). J Biol Chem 279: 31655–31663.

  • Morgan C, Pollard JW, Stanley ER . (1987). J Cell Physiol 130: 420–427.

  • Morley GM, Uden M, Gullick WJ, Dibb NJ . (1999). Oncogene 18: 3076–3084.

  • Mundy GR . (2002). Annu Rev Med 53: 337–354.

  • Murray LJ, Abrams TJ, Long KR, Ngai TJ, Olson LM, Hong W et al. (2003). Clin Exp Metastasis 20: 757–766.

  • Paez JG, Janne PA, Lee JC, Tracy S, Greulich H, Gabriel S et al. (2004). Science 304: 1497–1500.

  • Perry VH . (2004). Brain Behav Immun 18: 407–413.

  • Pollard JW . (1997). Mol Reprod Dev 46: 54–60; discussion 60–61.

  • Pollard JW . (2004). Nat Rev Cancer 4: 71–78.

  • Reilly JT . (2002). Br J Haematol 116: 744–757.

  • Rohrschneider LR, Metcalf D . (1989). Mol Cell Biol 9: 5081–5092.

  • Roussel MF, Downing JR, Rettenmier CW, Sherr CJ . (1988). Cell 55: 979–988.

  • Roussel MF, Dull TJ, Rettenmier CW, Ralph P, Ullrich A, Sherr CJ . (1987). Nature 325: 549–552.

  • Schindler T, Bornmann W, Pellicena P, Miller WT, Clarkson B, Kuriyan J . (2000). Science 289: 1938–1942.

  • Sherr CJ, Rettenmier CW, Sacca R, Roussel MF, Look AT, Stanley ER . (1985). Cell 41: 665–676.

  • Sweet MJ, Hume DA . (2003). Arch Immunol Ther Exp (Warsz) 51: 169–177.

  • Uden M, Morley GM, Dibb NJ . (1999). Oncogene 18: 3846–3851.

  • Wheeler EF, Askew D, May S, Ihle JN, Sherr CJ . (1987). Mol Cell Biol 7: 1673–1680.

  • Woolford J, McAuliffe A, Rohrschneider LR . (1988). Cell 55: 965–977.

  • Zermati Y, De Sepulveda P, Feger F, Letard S, Kersual J, Casteran N et al. (2003). Oncogene 22: 660–664.

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Acknowledgements

We thank Emma Davenport, Julia Frances, Junia Melo, John Maher, Malcolm Parker and Irene Roberts for their help and Anne Ridley and Richard Stanley for the Bacl.2F5 cell line. We also thank Chiron for providing M-CSF. JRT and NB are recipients of BBSRC studentships. JD acknowledges the support of an NKRF project Grant RP28/2/01.

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  1. Institute of Reproductive and Developmental Biology, Imperial College London, Hammersmith Campus, London, UK

    J R Taylor, N Brownlow & N J Dibb

  2. Division of Medicine, Imperial College London, Hammersmith Campus, London, UK

    J Domin

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  1. J R Taylor
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Correspondence to N J Dibb.

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Taylor, J., Brownlow, N., Domin, J. et al. FMS receptor for M-CSF (CSF-1) is sensitive to the kinase inhibitor imatinib and mutation of Asp-802 to Val confers resistance. Oncogene 25, 147–151 (2006). https://doi.org/10.1038/sj.onc.1209007

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