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

EK Grand, AJ Chase, C Heath, A Rahemtulla… - Leukemia, 2004 - nature.com
EK Grand, AJ Chase, C Heath, A Rahemtulla, NCP Cross
Leukemia, 2004nature.com
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 …
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, at (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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