1. Chronic myeloproliferative disorders with rearrangement of the platelet-derived growth factor α receptor: a new clinical target for STI571/Glivec
- Author
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Claire Villalva, Florence Armstrong, Georges Delsol, Pierre Brousset, Guy Laurent, Pascal Trempat, and Nicole Dastugue
- Subjects
Male ,Cancer Research ,Receptor, Platelet-Derived Growth Factor alpha ,Platelet-derived growth factor ,Chromosomes, Human, Pair 22 ,Fusion Proteins, bcr-abl ,PDGFRA ,Biology ,Piperazines ,Translocation, Genetic ,Exon ,chemistry.chemical_compound ,Growth factor receptor ,Leukemia, Myelogenous, Chronic, BCR-ABL Positive ,hemic and lymphatic diseases ,Genetics ,Humans ,Molecular Biology ,Gene Rearrangement ,Breakpoint ,breakpoint cluster region ,Middle Aged ,Pyrimidines ,Imatinib mesylate ,chemistry ,Benzamides ,Imatinib Mesylate ,Cancer research ,Chromosomes, Human, Pair 4 ,Tyrosine kinase - 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 alpha 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.
- Published
- 2003
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