Journal
HAEMATOLOGICA
Volume 93, Issue 1, Pages 49-56Publisher
FERRATA STORTI FOUNDATION
DOI: 10.3324/haematol.11836
Keywords
systemic mastocytosis; chronic basophilic leukemia; PRKG2-PDGFRB; imatinib
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Funding
- Intramural Research Program of the NIH, NIAID
- NCI Center for Cancer Research
- Foundation Against Cancer (a public interest foundation)
- K.U. Leuven
- NIH/NIAID Division of Intramural Research
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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). Design and 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-PDGFR beta 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.
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