Molecular Drug Targets in Myeloproliferative Neoplasms
Fibroblast Growth Factor Receptor and Platelet-Derived Growth Factor Receptor Abnormalities in Eosinophilic Myeloproliferative DisordersCross N.C.P.a · Reiter A.b
aWessex Regional Genetics Laboratory, University of Southampton, Salisbury District Hospital, Salisbury, UK; bIII. Medizinische Universitätsklinik, Medizinische Fakultät Mannheim der Universität Heidelberg, Mannheim, Germany
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Rearrangements of the genes encoding the fibroblast growth factor receptor 1 (FGFR1) and platelet-derived growth factor receptors (PDGFR) α or β 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.
© 2008 S. Karger AG, Basel
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