Myeloproliferative disorders: the centrosome connection.
Some myeloproliferative disorders (MPD) result from a reciprocal translocation that involves the FGFR1 gene and a partner gene. The event creates a chimeric gene that encodes a fusion protein with constitutive FGFR1 tyrosine kinase activity. FGFR1-MPD is a rare disease, but its study may provide interesting clues on different processes such as cell signalling, oncogenesis and stem cell renewal. Some partners of FGFR1 are centrosomal proteins. The corresponding oncogenic fusion kinases are targeted to the centrosome. Constitutive phosphorylation at this site may perturbate centrosome function and the cell cycle. Direct attack at this small organelle may be an efficient way for oncogenes to alter regulation of signalling for proliferation and survival and get rid of checkpoints in cell cycle progression. The same effect might be triggered by other fusion kinases in other MPD and non-MPD malignancies.
Delaval
B
B
Laboratory of Molecular Oncology, UMR599 Inserm, Marseille Cancer Institute, Institut Paoli-Calmettes, Marseille, France.
Lelièvre
H
H
Birnbaum
D
D
D002453:Cell Cycle; D018385:Centrosome / Q000502:physiology*; D006801:Humans; D009196:Myeloproliferative Disorders / Q000378:metabolism* / Q000473:pathology; D015514:Oncogene Proteins, Fusion / Q000502:physiology*; D010766:Phosphorylation; D020794:Receptor Protein-Tyrosine Kinases / Q000502:physiology*; D051496:Receptor, Fibroblast Growth Factor, Type 1; D017468:Receptors, Fibroblast Growth Factor / Q000502:physiology*
D015514:Oncogene Proteins, Fusion; D017468:Receptors, Fibroblast Growth Factor; C496348:FGFR1 protein, human; D020794:Receptor Protein-Tyrosine Kinases; D051496:Receptor, Fibroblast Growth Factor, Type 1