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KANK1, a candidate tumor suppressor gene, is fused to PDGFRB in an imatinib-responsive myeloid neoplasm with severe thrombocythemia

Leukemia volume 24, pages 1052–1055 (2010)Cite this article

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The majority of myeloproliferative neoplasms are associated with activating mutations in protein tyrosine kinase genes.1 About 20 different fusion products of the PDGFRB gene, which encodes platelet-derived growth factor receptor-β (PDGFRβ), have been described in patients with myeloid neoplasms associated with eosinophilia.1, 2 Myelodysplastic features and thrombocytopenia are often associated with PDGFRB translocations.3

Fluorescence in situ hybridization analysis established the disruption of the PDGFRB locus. As this tyrosine kinase receptor is highly sensitive to imatinib mesylate,2, 3 the patient was treated with a low dose of this drug (100 mg/day). At 4 months after the initiation of this treatment, platelet and leukocyte counts were back to normal levels (Figure 1b). After 12 months of follow-up, the patient remains in complete hematological remission. The response to low-dose imatinib pointed to constitutive activation of PDGFRβ as the cause of thrombocythemia in this patient.

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Acknowledgements

This work was supported by grants from the Salus Sanguinis foundation, the Bekales foundation and Action de Recherches Concertées (Communauté Française de Belgique). SM is the recipient of a fellowship from the Maurange foundation (managed by the Roi Baudouin foundation), FD is a FRS-FNRS research fellow and FT is supported by a scholarship from Opération Télévie. We wish to thank Jean-Luc Vaerman for providing samples and Catherine Marbehant for excellent technical assistance. We are grateful to Thomas Michiels for generous donations of reagents and to Laurent Knoops and Stefan Constantinescu for very helpful discussions. This study was approved by the ethics committee of the medical faculty (ref # F/2005/02). Informed consent was obtained.

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Author notes

  1. S Medves, F P Duhoux, H A Poirel and J-B Demoulin: These authors equally contributed to this work.

Authors and Affiliations

  1. de Duve Institute, Université catholique de Louvain, Brussels, Belgium

    S Medves, F Toffalini & J-B Demoulin

  2. Centre for Human Genetics, Cliniques universitaires Saint-Luc, Université catholique de Louvain, Brussels, Belgium

    F P Duhoux, G Ameye, J-M Libouton & H A Poirel

  3. Hematology Unit, Cliniques universitaires Saint-Luc, Université catholique de Louvain, Brussels, Belgium

    A Ferrant

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  1. S Medves
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Correspondence to J-B Demoulin.

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Medves, S., Duhoux, F., Ferrant, A. et al. KANK1, a candidate tumor suppressor gene, is fused to PDGFRB in an imatinib-responsive myeloid neoplasm with severe thrombocythemia. Leukemia 24, 1052–1055 (2010). https://doi.org/10.1038/leu.2010.13

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