Fibroblast growth factor receptor and platelet-derived growth factor receptor abnormalities in eosinophilic myeloproliferative disorders.
Rearrangements of the genes encoding the fibroblast growth factor receptor 1 (FGFR1) and platelet-derived growth factor receptors (PDGFR) alpha or beta receptor tyrosine kinases are found in a rare but important subset of patients with atypical myeloproliferative disorders that are usually but not always associated with eosinophilia. Chromosomal translocations or other rearrangements at 8p11-12, 4q12 or 5q31-33 give rise to diverse fusion genes encoding chimaeric proteins with constitutive transforming activity. There is considerable molecular heterogeneity with 8 partner genes currently known for FGFR1, 6 for PDGFRA and 17 for PDGFRB. The vast majority of patients with PDGFRA or PDGFRB fusions achieve rapid and durable complete haematological and molecular responses to sustained imatinib therapy. A key ongoing challenge is to define the molecular pathogenesis of the great majority of atypical myeloproliferative disorders for whom the causative lesion remains unknown, since very few of these cases gain any benefit from imatinib or other second-generation inhibitors.
Wessex Regional Genetics Laboratory, University of Southampton, Salisbury District Hospital, Salisbury, UK. ncpc@soton.ac.uk
Nicholas C P
NC
Cross
Andreas
A
Reiter
D000818:Animals; D001549:Benzamides; D002877:Chromosomes, Human / Q000235:genetics / Q000378:metabolism; D006801:Humans; D017681:Hypereosinophilic Syndrome / Q000188:drug therapy* / Q000201:enzymology / Q000235:genetics*; D000068877:Imatinib Mesylate; D015514:Oncogene Proteins, Fusion / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D010879:Piperazines / Q000627:therapeutic use*; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D011743:Pyrimidines / Q000627:therapeutic use*; D051496:Receptor, Fibroblast Growth Factor, Type 1 / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D020796:Receptor, Platelet-Derived Growth Factor alpha / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D020797:Receptor, Platelet-Derived Growth Factor beta / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D014178:Translocation, Genetic
D001549:Benzamides; D015514:Oncogene Proteins, Fusion; D010879:Piperazines; D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; D000068877:Imatinib Mesylate; C496348:FGFR1 protein, human; D051496:Receptor, Fibroblast Growth Factor, Type 1; D020796:Receptor, Platelet-Derived Growth Factor alpha; D020797:Receptor, Platelet-Derived Growth Factor beta