Preferred Name |
Signaling by FGFR1 fusion mutants |
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Synonyms |
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Definitions |
8p11 myeloproliferative syndrome (EMS) is an aggressive disorder that is associated with a translocation event at the FGFR1 gene on chromosome 8p11. Typical symptoms upon diagnosis include eosinophilia and associated T-cell lymphoblastic lymphoma; the disease rapidly advances to acute leukemia, usually of myeloid lineage. At present the only effective treatment is allogenic stem cell transplantation (reviewed in Jackson, 2010). <br><br>At the molecular level, EMS appears to be caused by translocation events on chromosome 8 that create gene fusions between the intracellular domain of FGFR1 and an N-terminal partner gene that encodes a dimerization domain. The resulting fusion protein dimerizes in a ligand-independent fashion based the N-terminal domain provided by the partner protein and stimulates constititutive downstream FGFR1 signaling without altering the intrisic kinase activity of the receptor. To date, 11 partner genes have been identified: ZMYM2, FGFR1OP, FGFR1OP2, HERVK, TRIM24, CUX1, BCR, CEP110, LRRFIP1, MYO18A and CPSF6, although not all have been functionally characterized (reviewed in Jackson, 2010, Turner and Grose, 2010; Wesche, 2011). <br>Where examined, cell lines carrying FGFR1 fusion genes have been shown to be transforming and to support IL3-independent proliferation through anti-apoptotic, prosurvival pathways(Lelièvre, 2008; Ollendorff, 1999; Chase, 2007; Guasch, 2001; Wasag 2011; Roumiantsev, 2004; Demiroglu, 2001; Smedley, 1999). Signaling appears to occur predominantly through PLCgamma, PI3K and STAT signaling, with a more minor contribution from MAPK activation. Because the fusion proteins lack the FRS2-binding site, the mechanism of MAPK activation is unclear. Recruitment of GRB2:SOS1 through recruitment of SHC is one possibility (Guasch, 2001). Edited: Rothfels, K, 2012-05-16 Authored: Rothfels, K, 2012-02-09 Reviewed: Ezzat, S, 2012-05-15 |
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ID |
http://purl.obolibrary.org/obo/HINO_0016292 |
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comment |
8p11 myeloproliferative syndrome (EMS) is an aggressive disorder that is associated with a translocation event at the FGFR1 gene on chromosome 8p11. Typical symptoms upon diagnosis include eosinophilia and associated T-cell lymphoblastic lymphoma; the disease rapidly advances to acute leukemia, usually of myeloid lineage. At present the only effective treatment is allogenic stem cell transplantation (reviewed in Jackson, 2010). Edited: Rothfels, K, 2012-05-16 Authored: Rothfels, K, 2012-02-09 Reviewed: Ezzat, S, 2012-05-15 |
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definition source |
Pubmed17698633 Pubmed20226962 Pubmed15050920 Pubmed21330321 Pubmed11739186 Reactome, http://www.reactome.org Pubmed21367659 Pubmed11689702 Pubmed18412956 Pubmed10935490 Pubmed21711248 Pubmed20094046 Pubmed10480903 |
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label |
Signaling by FGFR1 fusion mutants |
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located_in | ||
prefixIRI |
HINO:0016292 |
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prefLabel |
Signaling by FGFR1 fusion mutants |
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seeAlso |
Reactome Database ID Release 431839117 ReactomeREACT_121141 |
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subClassOf | ||
has_part |
http://purl.obolibrary.org/obo/HINO_0008618 http://purl.obolibrary.org/obo/HINO_0008626 http://purl.obolibrary.org/obo/HINO_0008625 http://purl.obolibrary.org/obo/HINO_0008627 http://purl.obolibrary.org/obo/HINO_0008621 http://purl.obolibrary.org/obo/HINO_0008624 http://purl.obolibrary.org/obo/HINO_0008117 http://purl.obolibrary.org/obo/HINO_0008110 http://purl.obolibrary.org/obo/HINO_0008114 http://purl.obolibrary.org/obo/HINO_0008113 http://purl.obolibrary.org/obo/HINO_0008112 http://purl.obolibrary.org/obo/HINO_0008111 http://purl.obolibrary.org/obo/HINO_0008116 http://purl.obolibrary.org/obo/HINO_0008118 http://purl.obolibrary.org/obo/HINO_0008115 |