| http://www.reactome.org/bio... | rdf:type | biopax3:Pathway | lld:biopax3 |
| http://www.reactome.org/bio... | biopax3:comment | Edited: Rothfels, K, 2012-05-16 | lld:biopax3 |
| http://www.reactome.org/bio... | biopax3:comment | Reviewed: Ezzat, S, 2012-05-15 | lld:biopax3 |
| http://www.reactome.org/bio... | biopax3:comment | Authored: Rothfels, K, 2012-02-09 | lld:biopax3 |
| http://www.reactome.org/bio... | biopax3: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). <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). | lld:biopax3 |
| http://www.reactome.org/bio... | biopax3:xref | http://identifiers.org/pubm... | lld:biopax3 |
| http://www.reactome.org/bio... | biopax3:xref | http://identifiers.org/pubm... | lld:biopax3 |
| http://www.reactome.org/bio... | biopax3:xref | http://identifiers.org/pubm... | lld:biopax3 |
| http://www.reactome.org/bio... | biopax3:xref | http://identifiers.org/pubm... | lld:biopax3 |
| http://www.reactome.org/bio... | biopax3:xref | http://identifiers.org/pubm... | lld:biopax3 |
| http://www.reactome.org/bio... | biopax3:xref | http://identifiers.org/pubm... | lld:biopax3 |
| http://www.reactome.org/bio... | biopax3:xref | http://identifiers.org/pubm... | lld:biopax3 |
| http://www.reactome.org/bio... | biopax3:xref | http://identifiers.org/pubm... | lld:biopax3 |
| http://www.reactome.org/bio... | biopax3:xref | http://identifiers.org/pubm... | lld:biopax3 |
| http://www.reactome.org/bio... | biopax3:xref | http://identifiers.org/pubm... | lld:biopax3 |
| http://www.reactome.org/bio... | biopax3:xref | http://identifiers.org/pubm... | lld:biopax3 |
| http://www.reactome.org/bio... | biopax3:xref | http://identifiers.org/pubm... | lld:biopax3 |
| http://www.reactome.org/bio... | biopax3:xref | urn:biopax:UnificationXref:... | lld:biopax3 |
| http://www.reactome.org/bio... | biopax3:xref | urn:biopax:UnificationXref:... | lld:biopax3 |
| http://www.reactome.org/bio... | biopax3:dataSource | urn:biopax:Provenance:react... | lld:biopax3 |
| http://www.reactome.org/bio... | biopax3:dataSource | http://www.reactome.org/bio... | lld:biopax3 |
| http://www.reactome.org/bio... | biopax3:displayName | Signaling by FGFR1 fusion mutants | lld:biopax3 |
| http://www.reactome.org/bio... | biopax3:organism | http://identifiers.org/taxo... | lld:biopax3 |
| http://www.reactome.org/bio... | biopax3:pathwayComponent | http://www.reactome.org/bio... | lld:biopax3 |
| http://www.reactome.org/bio... | biopax3:pathwayComponent | http://www.reactome.org/bio... | lld:biopax3 |
| http://www.reactome.org/bio... | biopax3:pathwayComponent | http://www.reactome.org/bio... | lld:biopax3 |
| http://www.reactome.org/bio... | biopax3:pathwayComponent | http://www.reactome.org/bio... | lld:biopax3 |
| http://www.reactome.org/bio... | biopax3:pathwayComponent | http://www.reactome.org/bio... | lld:biopax3 |
| http://www.reactome.org/bio... | biopax3:pathwayComponent | http://www.reactome.org/bio... | lld:biopax3 |
| http://www.reactome.org/bio... | biopax3:pathwayComponent | http://www.reactome.org/bio... | lld:biopax3 |
| http://www.reactome.org/bio... | biopax3:pathwayComponent | http://www.reactome.org/bio... | lld:biopax3 |
| http://www.reactome.org/bio... | biopax3:pathwayComponent | http://www.reactome.org/bio... | lld:biopax3 |
| http://www.reactome.org/bio... | biopax3:pathwayComponent | http://www.reactome.org/bio... | lld:biopax3 |
| http://www.reactome.org/bio... | biopax3:pathwayComponent | http://www.reactome.org/bio... | lld:biopax3 |
| http://www.reactome.org/bio... | biopax3:pathwayComponent | http://www.reactome.org/bio... | lld:biopax3 |
| http://www.reactome.org/bio... | biopax3:pathwayComponent | http://www.reactome.org/bio... | lld:biopax3 |
| http://www.reactome.org/bio... | biopax3:pathwayComponent | http://www.reactome.org/bio... | lld:biopax3 |
| http://www.reactome.org/bio... | biopax3:pathwayComponent | http://www.reactome.org/bio... | lld:biopax3 |
| http://www.reactome.org/bio... | biopax3:pathwayComponent | http://www.reactome.org/bio... | lld:biopax3 |
| http://www.reactome.org/bio... | biopax3:pathwayComponent | http://www.reactome.org/bio... | lld:biopax3 |
| http://www.reactome.org/bio... | biopax3:pathwayOrder | http://www.reactome.org/bio... | lld:biopax3 |
| http://www.reactome.org/bio... | biopax3:pathwayOrder | http://www.reactome.org/bio... | lld:biopax3 |
| http://www.reactome.org/bio... | biopax3:pathwayOrder | http://www.reactome.org/bio... | lld:biopax3 |
| http://www.reactome.org/bio... | biopax3:pathwayOrder | http://www.reactome.org/bio... | lld:biopax3 |
| http://www.reactome.org/bio... | biopax3:pathwayOrder | http://www.reactome.org/bio... | lld:biopax3 |
| http://www.reactome.org/bio... | biopax3:pathwayOrder | http://www.reactome.org/bio... | lld:biopax3 |
| http://www.reactome.org/bio... | biopax3:pathwayOrder | http://www.reactome.org/bio... | lld:biopax3 |
| http://www.reactome.org/bio... | biopax3:pathwayOrder | http://www.reactome.org/bio... | lld:biopax3 |
| http://www.reactome.org/bio... | biopax3:pathwayOrder | http://www.reactome.org/bio... | lld:biopax3 |
| http://www.reactome.org/bio... | biopax3:pathwayOrder | http://www.reactome.org/bio... | lld:biopax3 |
| http://www.reactome.org/bio... | biopax3:pathwayOrder | http://www.reactome.org/bio... | lld:biopax3 |
| http://www.reactome.org/bio... | biopax3:pathwayOrder | http://www.reactome.org/bio... | lld:biopax3 |
| http://www.reactome.org/bio... | biopax3:pathwayOrder | http://www.reactome.org/bio... | lld:biopax3 |
| http://www.reactome.org/bio... | biopax3:pathwayOrder | http://www.reactome.org/bio... | lld:biopax3 |
| http://www.reactome.org/bio... | biopax3:pathwayOrder | http://www.reactome.org/bio... | lld:biopax3 |
| http://www.reactome.org/bio... | biopax3:pathwayOrder | http://www.reactome.org/bio... | lld:biopax3 |
| http://www.reactome.org/bio... | biopax3:pathwayOrder | http://www.reactome.org/bio... | lld:biopax3 |
| http://www.reactome.org/bio... | biopax3:stepProcess | http://www.reactome.org/bio... | lld:biopax3 |
| http://www.reactome.org/bio... | biopax3:pathwayComponent | http://www.reactome.org/bio... | lld:biopax3 |
