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Characterization of three new imatinib-responsive fusion genes in chronic myeloproliferative disorders generated by disruption of the platelet-derived growth factor receptor beta gene

Walz, Christoph, Metzgeroth, Georgia, Haferlach, Claudia, Schmitt-Graeff, Annette, Fabarius, Alice, Hagen, Volker, Prummer, Otto, Rauh, Stefan, Hehlmann, Rüdiger, Hochhaus, Andreas, Cross, Nicholas C.P. and Reiter, Andreas (2007) Characterization of three new imatinib-responsive fusion genes in chronic myeloproliferative disorders generated by disruption of the platelet-derived growth factor receptor beta gene Haematologica, 92, (2), pp. 163-169. (doi:10.3324/haematol.10980).

Record type: Article


Background and Objectives: We sought to identify new fusion genes with involvement of the platelet-derived growth factor receptor ß gene (PDGFRB) in three patients presenting with various subtypes of chronic myeloproliferative disorders associated with chromosomal aberrations involving chromosome bands 5q31–33.
Design and Methods: We performed 5' rapid amplification of cDNA ends (5'-RACE)-polymerase chain reaction (PCR) with RNA/cDNA derived from a patient (case #1) with a t(5;12)(q31–33;q24) and a second patient (case #2) with a complex rearrangement involving chromosomes 1, 5 and 11. A newly developed DNA-based ‘longdistance inverse PCR’ (LDI-PCR) was performed on a third patient (case #3) with a t(4;5;5)(q23;q31;q33).
Results: In cases #1 and #2, we identified mRNA fusions between GIT2 exon 12 and GPIAP1 exon 7, respectively, and PDGFRB exon 11. In case #3, LDI-PCR revealed a fusion between PRKG2 exon 5 and a truncated PDGFRB exon 12. The region encoding the catalytic domain of PDGFRß is retained in all three cases, with the partner contributing a coiled-coil domain (GPIAP1, PRKG2) or an ankyrin protein interaction motif (GIT2) that may potentially lead to dimerization and constitutive activation of the fusion proteins. Treatment with imatinib (400 mg/day) has led to sustained complete hematologic remission in all three patients.
Interpretation and Conclusions: These data provide further evidence that numerous partner genes fuse to PDGFRB in BCR-ABL negative chronic myeloproliferative disorders. Although these fusion genes occur rarely, their identification is essential in order to detect patients in whom targeted treatment with tyrosine kinase inhibitors is likely to be successful.

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Published date: February 2007
Keywords: genetics, aged, research, female, chromosomes, drug therapy, middle aged, agents, gtpase-activating proteins, dimerization, methods, growth, treatment, transcription factors


Local EPrints ID: 60393
ISSN: 0390-6078
PURE UUID: 47b84246-ee48-491a-830c-16a78f38d947
ORCID for Nicholas C.P. Cross: ORCID iD

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Date deposited: 09 Sep 2008
Last modified: 17 Jul 2017 14:23

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Author: Christoph Walz
Author: Georgia Metzgeroth
Author: Claudia Haferlach
Author: Annette Schmitt-Graeff
Author: Alice Fabarius
Author: Volker Hagen
Author: Otto Prummer
Author: Stefan Rauh
Author: Rüdiger Hehlmann
Author: Andreas Hochhaus
Author: Andreas Reiter

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