FIP1L1-PDGFR alpha, a therapeutic target for the treatment of chronic eosinophilic leukemia.
The identification of the FIP1L1-PDGFRA fusion gene provides a molecular explanation for the pathogenesis of approximately half of the patients with the hypereosinophilic syndrome (HES). A diagnostic test to identify FIP1L1-PDGFRA positive HES cases (subsequently reclassified as chronic eosinophilic leukemia, CEL) is now available. FIP1L1-PDGFR alpha is a novel therapeutic target of the kinase inhibitor imatinib (Glivec, Novartis), which provides the basis for the treatment of these patients with this drug. FIP1L1-PDGFRA positive CEL patients respond very well to imatinib therapy, some of which are remarkable responses with normalization of the blood counts within 2 weeks after start of the therapy. Imatinib is well tolerated with minimal side effects, and most CEL patients respond to low doses of imatinib (100 mg/day), being important for lowering both the cost of therapy and drug related toxicity. All imatinib treated FIP1L1-PDGFRA positive CEL patients achieve hematological and cytogenetic remission, and the majority of patients also achieve a molecular remission with the fusion gene no longer detectable in blood, even by the most sensitive PCR techniques.
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D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001549:Benzamides; D002908:Chronic Disease; D006801:Humans; D017681:Hypereosinophilic Syndrome / Q000188:drug therapy* / Q000235:genetics*; D000068877:Imatinib Mesylate; D015514:Oncogene Proteins, Fusion; D010879:Piperazines / Q000627:therapeutic use*; D011743:Pyrimidines / Q000627:therapeutic use*; D020796:Receptor, Platelet-Derived Growth Factor alpha / Q000187:drug effects* / Q000235:genetics; D016896:Treatment Outcome; D039221:mRNA Cleavage and Polyadenylation Factors / Q000187:drug effects* / Q000235:genetics
D000970:Antineoplastic Agents; D001549:Benzamides; D015514:Oncogene Proteins, Fusion; D010879:Piperazines; D011743:Pyrimidines; D039221:mRNA Cleavage and Polyadenylation Factors; D000068877:Imatinib Mesylate; C479819:FIP1L1-PDGFRA fusion protein, human; D020796:Receptor, Platelet-Derived Growth Factor alpha