MYELOID NEOPLASIA Novel imatinib-sensitive PDGFRA-activating point mutations in hypereosinophilic syndrome induce growth factor independence and leukemia-like disease
نویسندگان
چکیده
1Department of Medicine A, Hematology, Oncology, and Pneumology, University of Münster, Münster, Germany; 2III Medizinische Klinik, Universitätsmedizin Mannheim, Universität Heidelberg, Mannheim, Germany; 3Max-Planck-Institute for Molecular Biomedicine, Münster, Germany; 4Department of Medicine, Hematology, and Oncology, University of Frankfurt, Frankfurt, Germany; 5Human Genetics Division, University of Southampton School of Medicine, Southampton, United Kingdom; and 6Abteilung Hämatologie/Onkologie, Universitätsklinikum Jena, Jena, Germany
منابع مشابه
Novel imatinib-sensitive PDGFRA-activating point mutations in hypereosinophilic syndrome induce growth factor independence and leukemia-like disease.
The FIP1L1-PDGFRA fusion is seen in a fraction of cases with a presumptive diagnosis of hypereosinophilic syndrome (HES). However, because most HES patients lack FIP1L1-PDGFRA, we studied whether they harbor activating mutations of the PDGFRA gene. Sequencing of 87 FIP1L1-PDGFRA-negative HES patients revealed several novel PDGFRA point mutations (R481G, L507P, I562M, H570R, H650Q, N659S, L705P,...
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Idiopathic hypereosinophilic syndrome (HES) and chronic eosinophilic leukemia (CEL) comprise a spectrum of indolent to aggressive diseases characterized by unexplained, persistent hypereosinophilia. These disorders have eluded a unique molecular explanation, and therapy has primarily been oriented toward palliation of symptoms related to organ involvement. Recent reports indicate that HES and C...
متن کاملThe FIP1L1-PDGFR fusion tyrosine kinase in hypereosinophilic syndrome and chronic eosinophilic leukemia: implications for diagnosis, classification, and management
Idiopathic hypereosinophilic syndrome (HES) and chronic eosinophilic leukemia (CEL) comprise a spectrum of indolent to aggressive diseases characterized by unexplained, persistent hypereosinophilia. These disorders have eluded a unique molecular explanation, and therapy has primarily been oriented toward palliation of symptoms related to organ involvement. Recent reports indicate that HES and C...
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Location 4q12 Protein Composed of an extracellular domain, a transmembrane domain, a juxtamembrane domain, and an intracellular domain; receptor tyrosine kinase; forms homodimer, and heterodimer with PDGFRB; dimerization induces kinase domain activation, leading to the activation of intracellular signalling pathways (Kawagishi et al., 1995). Somatic mutations Hybrid genes between various partne...
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Imatinib mesylate is a small molecule drug that in vitro inhibits the Abelson (Abl), Arg (abl-related gene), stem cell factor receptor (Kit), and platelet-derived growth factor receptor A and B (PDGFRA and PDGFRB) tyrosine kinases. The drug has acquired therapeutic relevance because of similar inhibitory activity against certain activating mutations of these molecular targets. The archetypical ...
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