Platelet-derived growth factor β (PDGFRβ), a tyrosine kinase receptor, has recently been shown to be constitutively activated by fusion to different gene partners in atypical, bcr-abl negative, myeloproliferative disorders. As a consequence, the activated PDGFRβ gene is a potential target for the tyrosine kinase inhibitor Imatinib mesylate. The objective of this study was to further characterise a t(5;9;14) translocation found in a 22 year old female patient with an atypical myeloproliferative characterised by eosinophilia, a severe paraneoplastic lichenoid eruption involving her skin and oral mucosa, and a poor response to conventional chemotherapy. G banded cytogenetic analysis of her bone marrow at diagnosis revealed an abnromal karyotype t(5;9;14)(q33;q22;q32) in 38 of 40 metaphases examined. There was no evidence of the bcr-abl fusion gene trancript by RT-PCR. Fluorescence in situ hybridisation using a CSF1-R probe suggested a breakpoint involving the PDGFRβ gene locus on chromosome 5q33 with an unknown partner gene on chromosome 14. 5′ RACE-PCR studies using a PDGFRβ primer generated a product of 220bp that on sequencing revealed a novel gene KIAA1509 fused in frame to the 3′ end of PDGFRβ in exon 11. KIAA1509 has previously been mapped to chromosome 14 and encodes a protein of 1935 amino acids that shows homology to HOOK proteins and contains coiled coiled domains. The resulting fusion protein preserves the tyrosine kinase domains of PDGFRβ, but lacks the transmembrane domain, and would be predicted to result in constitutive activation of the tyrosine kinase receptor. In view of these molecular findings, the patient was commenced on Imatinib mesylate, which resulted in a rapid haematologic response, including resolution of the mucosal and cutaneous manifestations, and a complete cytogenetic response after 3 months therapy. These findings highlight the importance of investigating the molecular basis of the myeloproliferative disorders to identify potential novel targets for Imatinib and similar molecules.

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