title: Activity of imatinib in systemic mastocytosis with chronic basophilic leukemia and a PRKG2-PDGFRB fusion.
abstract: BACKGROUND
  Translocations involving region 5q31-32 (PDGFRB) have been reported in a variety of myeloproliferative diseases and are often associated with significant peripheral eosinophilia. We report an unusual case of a patient presenting with peripheral basophilia and systemic mastocytosis in whom cytogenetic analysis revealed a t(4;5)(q21.1;q31.3).
  
  
  METHODS
  We used molecular analyses to determine the role of PDGFRB in this case. The patient was treated with imatinib.
  
  
  RESULTS
  Fluorescence in situ hybridization (FISH) documented a breakpoint in PDGFRB. In agreement with this, the patient responded very well to imatinib with resolution of clinical symptoms, basophilia, and mast cell disease. Molecular analyses revealed that PDGFRB, encoding an imatinib-sensitive tyrosine kinase, was fused to PRKG2. The fusion gene incorporates the first two exons of PRKG2 fused to the truncated exon 12 of PDGFRB, resulting in the disruption of its juxtamembrane domain. Functional studies confirmed that the activity and transforming properties of PRKG2-PDGFRbeta were dependent on the disruption of the auto-inhibitory juxtamembrane domain.
  
  
  CONCLUSIONS
  Our results identify a second case of the PRKG2-PDGFRB fusion and confirm the unusual PDGFRB breakpoint associated with this fusion. This work also illustrates the use of imatinib for the treatment of specific cases of systemic mastocytosis.
authors.affiliation: Human Genome Laboratory, Department of Molecular and Developmental Genetics, VIB, Leuven, Belgium.
authors.forename: Idoya
authors.initials: I
authors.lastname: Lahortiga
authors.forename: Cem
authors.initials: C
authors.lastname: Akin
authors.forename: Jan
authors.initials: J
authors.lastname: Cools
authors.forename: Todd M
authors.initials: TM
authors.lastname: Wilson
authors.forename: Nicole
authors.initials: N
authors.lastname: Mentens
authors.forename: Diane C
authors.initials: DC
authors.lastname: Arthur
authors.forename: Irina
authors.initials: I
authors.lastname: Maric
authors.forename: Pierre
authors.initials: P
authors.lastname: Noel
authors.forename: Can
authors.initials: C
authors.lastname: Kocabas
authors.forename: Peter
authors.initials: P
authors.lastname: Marynen
authors.forename: Lawrence S
authors.initials: LS
authors.lastname: Lessin
authors.forename: Iwona
authors.initials: I
authors.lastname: Wlodarska
authors.forename: Jamie
authors.initials: J
authors.lastname: Robyn
authors.forename: Dean D
authors.initials: DD
authors.lastname: Metcalfe
mesh_terms: D000818:Animals; D001549:Benzamides; D001853:Bone Marrow / Q000473:pathology; D003582:Cytogenetics; D015973:Gene Expression Regulation, Leukemic; D006801:Humans; D000068877:Imatinib Mesylate; D016130:Immunophenotyping; D017404:In Situ Hybridization, Fluorescence; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000150:complications / Q000188:drug therapy* / Q000235:genetics*; D008297:Male; D034721:Mastocytosis, Systemic / Q000150:complications / Q000188:drug therapy* / Q000235:genetics*; D051379:Mice; D008875:Middle Aged; D015514:Oncogene Proteins, Fusion / Q000235:genetics*; D010879:Piperazines / Q000494:pharmacology*; D011743:Pyrimidines / Q000494:pharmacology*; D020797:Receptor, Platelet-Derived Growth Factor beta / Q000737:chemistry*
chemical_list: D001549:Benzamides; D015514:Oncogene Proteins, Fusion; D010879:Piperazines; D011743:Pyrimidines; D000068877:Imatinib Mesylate; D020797:Receptor, Platelet-Derived Growth Factor beta