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Ectopic expression of wild-type FGFR3 cooperates with MYC to accelerate development of B-cell lineage neoplasms
Journal article   Open access   Peer reviewed

Ectopic expression of wild-type FGFR3 cooperates with MYC to accelerate development of B-cell lineage neoplasms

A Zingone, Cm Cultraro, D-M Shin, Cm Bean, Hc Morse, S Janz and Wm Kuehl
Leukemia, Vol.24(6), pp.1171-1178
04/15/2010
DOI: 10.1038/leu.2010.50
PMCID: PMC3118571
PMID: 20393505
url
https://doi.org/10.1038/leu.2010.50View
Published (Version of record) Open Access

Abstract

The t(4;14) translocation in multiple myeloma (MM) simultaneously dysregulates two apparent oncogenes: fibroblast growth factor receptor 3 (FGFR3) controlled by the 3′ immunoglobulin heavy chain enhancer on der(14) and MMSET controlled by the intronic Eμ enhancer on der(4). Although all MM tumors and cell lines with a t(4;14) translocation have dysregulated MMSET, about 25% do not express FGFR3. Therefore, the function of dysregulated wild-type (WT) FGFR3 in the pathogenesis of MM remains unclear. We developed a murine transgenic (TG) model in which WT FGFR3 is over-expressed in B lymphoid cells. Although high levels of FGFR3 resulted in lymphoid hyperplasia in about one-third of older mice, no increase in tumorigenesis was observed. However, double TG FGFR3/Myc mice develop mature B lymphoma tumors that occur with a higher penetrance and shorter latency than in single TG Myc mice (P = 0.006). We conclude that expression of high levels of WT FGFR3 can be oncogenic and cooperate with MYC to generate B lymphoid tumors. This suggests that dysregulated FGFR3 expression is likely to be essential at least for the early stages of pathogenesis of MM tumors that have a t(4;14) translocation.
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