title: Durable responses to imatinib in patients with PDGFRB fusion gene-positive and BCR-ABL-negative chronic myeloproliferative disorders.
abstract: Fusion genes derived from the platelet-derived growth factor receptor beta (PDGFRB) or alpha (PDGFRA) play an important role in the pathogenesis of BCR-ABL-negative chronic myeloproliferative disorders (CMPDs). These fusion genes encode constitutively activated receptor tyrosine kinases that can be inhibited by imatinib. Twelve patients with BCR-ABL-negative CMPDs and reciprocal translocations involving PDGFRB received imatinib for a median of 47 months (range, 0.1-60 months). Eleven had prompt responses with normalization of peripheral-blood cell counts and disappearance of eosinophilia; 10 had complete resolution of cytogenetic abnormalities and decrease or disappearance of fusion transcripts as measured by reverse transcriptase-polymerase chain reaction (RT-PCR). Updates were sought from 8 further patients previously described in the literature; prompt responses were described in 7 and persist in 6. Our data show that durable hematologic and cytogenetic responses are achieved with imatinib in patients with PDGFRB fusion-positive, BCR-ABL-negative CMPDs.
authors.affiliation: Department of Haematology, University of Pecs, Pecs, Hungary.
authors.forename: Marianna
authors.initials: M
authors.lastname: David
authors.forename: Nicholas C P
authors.initials: NC
authors.lastname: Cross
authors.forename: Sonja
authors.initials: S
authors.lastname: Burgstaller
authors.forename: Andrew
authors.initials: A
authors.lastname: Chase
authors.forename: Claire
authors.initials: C
authors.lastname: Curtis
authors.forename: Raymond
authors.initials: R
authors.lastname: Dang
authors.forename: Martine
authors.initials: M
authors.lastname: Gardembas
authors.forename: John M
authors.initials: JM
authors.lastname: Goldman
authors.forename: Francis
authors.initials: F
authors.lastname: Grand
authors.forename: George
authors.initials: G
authors.lastname: Hughes
authors.forename: Francoise
authors.initials: F
authors.lastname: Huguet
authors.forename: Louise
authors.initials: L
authors.lastname: Lavender
authors.forename: Grant A
authors.initials: GA
authors.lastname: McArthur
authors.forename: Francois X
authors.initials: FX
authors.lastname: Mahon
authors.forename: Giorgio
authors.initials: G
authors.lastname: Massimini
authors.forename: Junia
authors.initials: J
authors.lastname: Melo
authors.forename: Philippe
authors.initials: P
authors.lastname: Rousselot
authors.forename: Robin J
authors.initials: RJ
authors.lastname: Russell-Jones
authors.forename: John F
authors.initials: JF
authors.lastname: Seymour
authors.forename: Graeme
authors.initials: G
authors.lastname: Smith
authors.forename: Alastair
authors.initials: A
authors.lastname: Stark
authors.forename: Katherine
authors.initials: K
authors.lastname: Waghorn
authors.forename: Zariana
authors.initials: Z
authors.lastname: Nikolova
authors.forename: Jane F
authors.initials: JF
authors.lastname: Apperley
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001549:Benzamides; D014408:Biomarkers, Tumor / Q000097:blood; D002648:Child; D002675:Child, Preschool; D004341:Drug Evaluation; D004802:Eosinophilia / Q000209:etiology; D005260:Female; D005500:Follow-Up Studies; D016044:Fusion Proteins, bcr-abl / Q000097:blood*; D006801:Humans; D000068877:Imatinib Mesylate; D007223:Infant; D054438:Leukemia, Myeloid, Chronic, Atypical, BCR-ABL Negative / Q000097:blood / Q000188:drug therapy / Q000235:genetics; D008297:Male; D008875:Middle Aged; D009196:Myeloproliferative Disorders / Q000097:blood / Q000188:drug therapy* / Q000235:genetics; D015514:Oncogene Proteins, Fusion / Q000097:blood* / Q000235:genetics; D010879:Piperazines / Q000627:therapeutic use*; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D011743:Pyrimidines / Q000627:therapeutic use*; D012333:RNA, Messenger / Q000097:blood; D012334:RNA, Neoplasm / Q000097:blood; D020797:Receptor, Platelet-Derived Growth Factor beta / Q000097:blood* / Q000235:genetics; D012189:Retrospective Studies; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014178:Translocation, Genetic; D016896:Treatment Outcome; D000097764:ETS Translocation Variant 6 Protein
chemical_list: D000970:Antineoplastic Agents; D001549:Benzamides; D014408:Biomarkers, Tumor; D016044:Fusion Proteins, bcr-abl; D000068877:Imatinib Mesylate; D015514:Oncogene Proteins, Fusion; D010879:Piperazines; D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D020797:Receptor, Platelet-Derived Growth Factor beta; C464679:ETV6-PDGFRB fusion protein, human; D000097764:ETS Translocation Variant 6 Protein