title: Recurrent CEP85L-PDGFRB fusion in patient with t(5;6) and imatinib-responsive myeloproliferative neoplasm with eosinophilia.
abstract: Fusion genes involving the catalytic domain of tyrosine kinases (TKs) play an important role in the pathogenesis of hematological malignancies and solid tumors. In BCR-ABL1-negative myeloproliferative neoplasms (MPNs) several different tyrosine kinase fusion events have been described, most commonly involving the genes encoding the platelet-derived growth factor receptor alpha (PDGFRA) or beta (PDGFRB). Since the introduction of small molecule kinase inhibitors, TK fusions have emerged as prime therapeutic targets. Here, we report a recurrent CEP85L-PDGFRB fusion in a patient with eosinophilia and an MPN. The fusion was confirmed by specific amplification of the genomic breakpoints and reverse transcription polymerase chain reaction (PCR). The patient was treated with imatinib and achieved hematologic and cytogenetic remission. Minimal residual disease screening over 3 years with nested PCR failed to detect CEP85L-PDGFRB mRNA or genomic DNA, confirming a long-term molecular remission on imatinib.
authors.affiliation: Wessex Regional Genetics Laboratory, Salisbury, UK.
authors.forename: Nils
authors.initials: N
authors.lastname: Winkelmann
authors.forename: Claire
authors.initials: C
authors.lastname: Hidalgo-Curtis
authors.forename: Katherine
authors.initials: K
authors.lastname: Waghorn
authors.forename: Joannah
authors.initials: J
authors.lastname: Score
authors.forename: Helen
authors.initials: H
authors.lastname: Dickinson
authors.forename: Andrew
authors.initials: A
authors.lastname: Jack
authors.forename: Sahra
authors.initials: S
authors.lastname: Ali
authors.forename: Nicholas C P
authors.initials: NC
authors.lastname: Cross
mesh_terms: D000595:Amino Acid Sequence; D000970:Antineoplastic Agents / Q000627:therapeutic use; D001483:Base Sequence; D001549:Benzamides / Q000627:therapeutic use; D056905:Chromosome Breakpoints; D002895:Chromosomes, Human, Pair 5; D002896:Chromosomes, Human, Pair 6; D004802:Eosinophilia / Q000150:complications*; D006801:Humans; D000068877:Imatinib Mesylate; D008297:Male; D008875:Middle Aged; D009196:Myeloproliferative Disorders / Q000150:complications* / Q000188:drug therapy / Q000235:genetics*; D015514:Oncogene Proteins, Fusion / Q000235:genetics*; D010879:Piperazines / Q000627:therapeutic use; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use; D011743:Pyrimidines / Q000627:therapeutic use; D020796:Receptor, Platelet-Derived Growth Factor alpha / Q000235:genetics*; D020797:Receptor, Platelet-Derived Growth Factor beta / Q000235:genetics*; D014178:Translocation, Genetic; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D001549:Benzamides; D015514:Oncogene Proteins, Fusion; D010879:Piperazines; D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; D000068877:Imatinib Mesylate; C586185:CEP85L-PDGFRB fusion protein; D020796:Receptor, Platelet-Derived Growth Factor alpha; D020797:Receptor, Platelet-Derived Growth Factor beta