title: Two novel imatinib-responsive PDGFRA fusion genes in chronic eosinophilic leukaemia.
abstract: We identified two patients with a t(2;4)(p24;q12) and a t(4;12)(q2?3;p1?2), respectively, in association with BCR-ABL and FIP1L1-PDGFRA negative chronic eosinophilic leukaemia. Molecular analysis revealed a novel STRN-PDGFRA fusion for the t(2;4) and ETV6-PDGFRA for the t(4;12). The fusions were confirmed by specific amplification of the genomic breakpoints, reverse transcription polymerase chain reaction and fluorescence in situ hybridisation. Both patients were treated with imatinib and, following a rapid haematological response, achieved cytogenetic remission and a major molecular response. In conclusion, PDGFRA fuses to diverse partner genes in myeloid disorders. Identification of these fusions is important as they are particularly sensitive to imatinib.
authors.affiliation: Wessex Regional Genetics Laboratory, University of Southampton, Salisbury, UK.
authors.forename: Claire E
authors.initials: CE
authors.lastname: Curtis
authors.forename: Francis H
authors.initials: FH
authors.lastname: Grand
authors.forename: Pellegrino
authors.initials: P
authors.lastname: Musto
authors.forename: Andrew
authors.initials: A
authors.lastname: Clark
authors.forename: John
authors.initials: J
authors.lastname: Murphy
authors.forename: Gianni
authors.initials: G
authors.lastname: Perla
authors.forename: Maria M
authors.initials: MM
authors.lastname: Minervini
authors.forename: Janet
authors.initials: J
authors.lastname: Stewart
authors.forename: Andreas
authors.initials: A
authors.lastname: Reiter
authors.forename: Nicholas C P
authors.initials: NC
authors.lastname: Cross
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001549:Benzamides; D002148:Calmodulin-Binding Proteins / Q000235:genetics; D002881:Chromosomes, Human, Pair 12; D002889:Chromosomes, Human, Pair 2; D002894:Chromosomes, Human, Pair 4; D006801:Humans; D017681:Hypereosinophilic Syndrome / Q000188:drug therapy / Q000235:genetics*; D000068877:Imatinib Mesylate; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D008565:Membrane Proteins / Q000235:genetics; D008875:Middle Aged; D009419:Nerve Tissue Proteins / Q000235:genetics; D050596:Oncogene Fusion; D010879:Piperazines / Q000627:therapeutic use*; D050783:Proto-Oncogene Proteins c-ets / Q000235:genetics; D011743:Pyrimidines / Q000627:therapeutic use*; D020796:Receptor, Platelet-Derived Growth Factor alpha / Q000235:genetics*; D012097:Repressor Proteins / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014178:Translocation, Genetic; D000097764:ETS Translocation Variant 6 Protein
chemical_list: D000970:Antineoplastic Agents; D001549:Benzamides; D002148:Calmodulin-Binding Proteins; D000068877:Imatinib Mesylate; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D010879:Piperazines; D050783:Proto-Oncogene Proteins c-ets; D011743:Pyrimidines; D020796:Receptor, Platelet-Derived Growth Factor alpha; D012097:Repressor Proteins; D000097764:ETS Translocation Variant 6 Protein; C491925:STRN protein, human