title: Recent breakthroughs in the understanding and management of chronic eosinophilic leukemia.
abstract: The term hypereosinophilic syndrome (HES) was initially introduced to describe a group of diseases all characterized by persistent unexplained hypereosinophilia. Additional names have subsequently been introduced to describe specific variants of HES, such as the myeloid variant and the lymphoid variant, or to indicate idiopathic HES, for which the cause of the eosinophilia is completely unknown. Molecular analysis led to the identification of the clonal origin of several subgroups of HES, clearly establishing these diseases as true leukemias. These cases of hypereosinophilia are now referred to as 'myeloid neoplasms associated with eosinophilia and abnormalities of PDGF receptor A and B (PDGFRA and PDGFRB), or FGF receptor 1 (FGFR1)'. In cases for which clonality is clear, but no PDGFRA, PDGFRB or FGFR1 rearrangement could be demonstrated, the term 'chronic eosinophilic leukemia, not otherwise specified' is preferred. Most importantly, patients with rearrangements of PDGFRA or PDGFRB can be efficiently treated with the kinase inhibitor imatinib. Additional potent kinase inhibitors have been identified, also including inhibitors that target FGFR1 and imatinib-resistant variants of PDGFRalpha. For treatment of unexplained hypereosinophilia and 'chronic eosinophilic leukemia, not otherwise specified; different therapeutic strategies are currently under investigation and promising results have been obtained using humanized anti-IL-5 antibodies. Further molecular understanding of the cause of these 'idiopathic' diseases may lead to the development of novel targeted therapies.
authors.affiliation: Department of Molecular and Developmental Genetics VIB11, Center for Human Genetics, KULeuven, Campus Gasthuisberg O&N1, Herestraat 49-box 602, B-3000 Leuven, Belgium. els.lierman@med.kuleuven.be
authors.forename: Els
authors.initials: E
authors.lastname: Lierman
authors.forename: Jan
authors.initials: J
authors.lastname: Cools
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D001549:Benzamides; D002908:Chronic Disease; D016503:Drug Delivery Systems; D006801:Humans; D017681:Hypereosinophilic Syndrome / Q000188:drug therapy* / Q000473:pathology; D000068877:Imatinib Mesylate; D015848:Interleukin-5 / Q000037:antagonists & inhibitors; D010879:Piperazines / Q000494:pharmacology / Q000627:therapeutic use; D047428:Protein Kinase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D011743:Pyrimidines / Q000494:pharmacology / Q000627:therapeutic use
chemical_list: D000970:Antineoplastic Agents; D001549:Benzamides; D015848:Interleukin-5; D010879:Piperazines; D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; D000068877:Imatinib Mesylate