title: FOP-FGFR1 tyrosine kinase, the product of a t(6;8) translocation, induces a fatal myeloproliferative disease in mice.
abstract: 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.
authors.affiliation: Institut National de la Santé et de la Recherche Médicale (INSERM), Marseille, France.
authors.forename: Geraldine
authors.initials: G
authors.lastname: Guasch
authors.forename: Bénédicte
authors.initials: B
authors.lastname: Delaval
authors.forename: Christine
authors.initials: C
authors.lastname: Arnoulet
authors.forename: Min-Jue
authors.initials: MJ
authors.lastname: Xie
authors.forename: Luc
authors.initials: L
authors.lastname: Xerri
authors.forename: Danielle
authors.initials: D
authors.lastname: Sainty
authors.forename: Daniel
authors.initials: D
authors.lastname: Birnbaum
authors.forename: Marie-Joséphe
authors.initials: MJ
authors.lastname: Pébusque
mesh_terms: 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
chemical_list: 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