title: Chronic myeloproliferative disorders with rearrangement of the platelet-derived growth factor alpha receptor: a new clinical target for STI571/Glivec.
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.
authors.affiliation: INSERM U563 'Centre de Physiopathologie de Toulouse-Purpan', Purpan Hospital, Toulouse, France.
authors.forename: Pascal
authors.initials: P
authors.lastname: Trempat
authors.forename: Claire
authors.initials: C
authors.lastname: Villalva
authors.forename: Guy
authors.initials: G
authors.lastname: Laurent
authors.forename: Florence
authors.initials: F
authors.lastname: Armstrong
authors.forename: Georges
authors.initials: G
authors.lastname: Delsol
authors.forename: Nicole
authors.initials: N
authors.lastname: Dastugue
authors.forename: Pierre
authors.initials: P
authors.lastname: Brousset
mesh_terms: D001549:Benzamides; D002892:Chromosomes, Human, Pair 22; D002894:Chromosomes, Human, Pair 4; D016044:Fusion Proteins, bcr-abl / Q000235:genetics; D015321:Gene Rearrangement; D006801:Humans; D000068877:Imatinib Mesylate; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D010879:Piperazines / Q000494:pharmacology*; D011743:Pyrimidines / Q000494:pharmacology*; D020796:Receptor, Platelet-Derived Growth Factor alpha / Q000037:antagonists & inhibitors* / Q000235:genetics*; D014178:Translocation, Genetic
chemical_list: D001549:Benzamides; D010879:Piperazines; D011743:Pyrimidines; D000068877:Imatinib Mesylate; D020796:Receptor, Platelet-Derived Growth Factor alpha; D016044:Fusion Proteins, bcr-abl