FOP-FGFR1 tyrosine kinase, the product of a t(6;8) translocation, induces a fatal myeloproliferative disease in mice.
Constitutive activation of aberrant fibroblast growth factor receptor 1 (FGFR1) kinase as a consequence of gene fusion such as FOP-FGFR1 associated with t(6; 8)(q27;p11-12) translocation, is the hallmark of an atypical aggressive stem cell myeloproliferative disorder (MPD) in humans. In this study, we show that expression of FOP-FGFR1 in primary bone marrow cells induced by retroviral transduction generates a MPD in mice. Constitutive FOP-FGFR1 kinase activity was both essential and sufficient to cause a chronic myeloproliferative syndrome in the murine bone marrow transplantation model. In contrast to the human disorder, lymphoproliferation and progression to acute phase were not observed. Lymphoid symptoms, however, appeared when onset of the disease was delayed as the result of mutation of FOP-FGFR1 at tyrosine 511, the phospholipase C gamma (PLCgamma) binding site.
Guasch
Geraldine
G
Institut National de la Santé et de la Recherche Médicale (INSERM), Marseille, France.
Delaval
Bénédicte
B
Arnoulet
Christine
C
Xie
Min-Jue
MJ
Xerri
Luc
L
Sainty
Danielle
D
Birnbaum
Daniel
D
Pébusque
Marie-Joséphe
MJ
D000818:Animals; D016026:Bone Marrow Transplantation; D002471:Cell Transformation, Neoplastic / Q000235:genetics; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009154:Mutation; D009196:Myeloproliferative Disorders / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D015514:Oncogene Proteins, Fusion / Q000235:genetics* / Q000378:metabolism*; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics* / Q000378:metabolism*; D051496:Receptor, Fibroblast Growth Factor, Type 1; D017468:Receptors, Fibroblast Growth Factor / Q000235:genetics* / Q000378:metabolism*; D014161:Transduction, Genetic; D014178:Translocation, Genetic
C439709:FOP-FGFR1 fusion protein, human; D015514:Oncogene Proteins, Fusion; D017468:Receptors, Fibroblast Growth Factor; C496348:FGFR1 protein, human; C496349:Fgfr1 protein, mouse; D020794:Receptor Protein-Tyrosine Kinases; D051496:Receptor, Fibroblast Growth Factor, Type 1