Ectopic expression of wild-type FGFR3 cooperates with MYC to accelerate development of B-cell lineage neoplasms. Leukemia 2010 Jun;24(6):1171-8
Date
04/16/2010Pubmed ID
20393505Pubmed Central ID
PMC3118571DOI
10.1038/leu.2010.50Scopus ID
2-s2.0-77954603996 (requires institutional sign-in at Scopus site) 20 CitationsAbstract
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 Emu 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 overexpressed 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.
Author List
Zingone A, Cultraro CM, Shin DM, Bean CM, Morse HC 3rd, Janz S, Kuehl WMAuthor
Siegfried Janz MD Professor in the Medicine department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AnimalsBiomarkers, Tumor
Blotting, Southern
Blotting, Western
Female
Gene Expression Profiling
Genes, Immunoglobulin
Humans
Immunoenzyme Techniques
Immunophenotyping
Immunoprecipitation
Lymphoma, B-Cell
Male
Mice
Mice, Transgenic
Multiple Myeloma
Oligonucleotide Array Sequence Analysis
Proto-Oncogene Proteins c-myc
RNA, Messenger
Receptor, Fibroblast Growth Factor, Type 3
Reverse Transcriptase Polymerase Chain Reaction