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Targeting FGFR3 in multiple myeloma: inhibition of t(4;14)-positive cells by SU5402 and PD173074

Leukemia volume 18, pages 962–966 (2004)Cite this article

Abstract

The t(4;14)(p16.3;q32), associated with 10–20% of cases of multiple myeloma (MM), deregulates the expression of MMSET and FGFR3. To assess the potential of FGFR3 as a drug target, we evaluated the effects of selective inhibitors on MM and control cell lines. SU5402 and PD173074 specifically inhibited the growth of the two t(4;14)-positive MM lines, KMS-11 and OPM-2. Importantly, inhibition was still observed in the presence of IL-6, a growth factor known to play an important role in MM. Both compounds induced a dose-dependent reduction in cell viability and an increase in apoptosis, accompanied by a decrease in extracellular signal-related kinase phosphorylation. In contrast, no inhibition was seen with either compound against t(4;14)-negative cell lines or NCI-H929, a t(4;14)-positive, FGFR3-negative MM cell line. FGFR3 is thus a plausible candidate for targeted therapy in a subset of MM patients.

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Acknowledgements

This work was supported by the British Society of Haematology Research Trust and the Leukaemia Research Fund.

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Authors and Affiliations

  1. Wessex Regional Genetics Laboratory, Salisbury, UK

    E K Grand, A J Chase & N C P Cross

  2. Department of Haematology, Faculty of Medicine, Imperial College, London, UK

    E K Grand, C Heath & A Rahemtulla

  3. Human Genetics Division, University of Southampton School of Medicine, Southampton, UK

    A J Chase & N C P Cross

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  1. E K Grand
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  2. A J Chase
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  4. A Rahemtulla
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Correspondence to N C P Cross.

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Grand, E., Chase, A., Heath, C. et al. Targeting FGFR3 in multiple myeloma: inhibition of t(4;14)-positive cells by SU5402 and PD173074. Leukemia 18, 962–966 (2004). https://doi.org/10.1038/sj.leu.2403347

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