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Chronic myeloproliferative disorders with rearrangement of the platelet-derived growth factor α receptor: a new clinical target for STI571/Glivec

Oncogene volume 22, pages 5702–5706 (2003)Cite this article

Abstract

Two cases of atypical chronic myeloid leukaemia (CML) carrying the t(4;22)(q12;q11) translocation involving the breakpoint cluster region (BCR) and platelet-derived growth factor α receptor (PDGFRA) genes have been recently characterized. We report a third case of atypical CML with the same translocation but with a distinct breakpoint fusing BCR exon 1 with PDGFRA exon 13. The patient had a clinical presentation of CML with progressive transformation in B-cell acute lymphoblastic leukaemia. The involvement of PDGFRA led us to treat the patient with the small organic compound imatinib mesylate/STI571 (Glivec) that blocks the ATP binding site of tyrosine kinases such as Abelson, KIT and platelet-derived growth factor receptors. The patient subsequently achieved a rapid clinical and molecular response clearly demonstrating, for the first time, that Glivec is active against PDGFRA in vivo. Therefore, our study expands the list of Glivec targets and has direct biological and also clinical implications.

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Acknowledgements

Génopôle Santé Toulouse, France and Association pour la Recherche sur le Cancer (ARC) contract no 4233 and ARECA Network ‘Proteomics and Cancer’.

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Authors and Affiliations

  1. INSERM U563 ‘Centre de Physiopathologie de Toulouse-Purpan’, Purpan Hospital, Toulouse, France

    Pascal Trempat, Claire Villalva, Florence Armstrong, Georges Delsol & Pierre Brousset

  2. Department of Pathology, Purpan Hospital, Toulouse, France

    Pascal Trempat, Claire Villalva, Florence Armstrong, Georges Delsol & Pierre Brousset

  3. Department of Haematology, Purpan Hospital, Toulouse, France

    Guy Laurent

  4. Department of Cytogenetics, Purpan Hospital, Toulouse, France

    Nicole Dastugue

Authors
  1. Pascal Trempat
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  2. Claire Villalva
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  4. Florence Armstrong
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  5. Georges Delsol
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Correspondence to Pierre Brousset.

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Trempat, P., Villalva, C., Laurent, G. et al. Chronic myeloproliferative disorders with rearrangement of the platelet-derived growth factor α receptor: a new clinical target for STI571/Glivec. Oncogene 22, 5702–5706 (2003). https://doi.org/10.1038/sj.onc.1206543

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