11Eosinophilic disorders: Molecular pathogenesis, new classification, and modern therapy
Section snippets
Clonality studies in hypereosinophilia
One method for establishing a diagnosis of CEL is demonstration of the clonal origin of eosinophils; however, this is frequently not assessed or difficult to confirm in patients lacking cytogenetic abnormalities. Methods for demonstrating clonality include fluorescent in situ hybridization,5 cytogenetic analysis of purified eosinophils,6 and X-chromosome inactivation analysis in females.7, 8 X-inactivation-based assessment of clonality is of limited value in HES because of the predominance of
Reactive and clonal eosinophilia associated with hematologic malignancies
Reactive eosinophilia can be observed with several hematologic malignancies. Eosinophilia is thought to result from the production of cytokines (e.g. IL-3, IL-5, and GM-CSF) from malignant cells in T-cell lymphomas,13 Hodgkin's disease,14 and acute lymphoblastic leukemias.15, 16 Eosinophilia might herald the initial diagnosis or relapse of these conditions.
The list of chromosomal abnormalities in literature-described cases of HES or CEL has grown considerably over the last 30 years. Bain
Biology of the platelet-derived growth factor receptors (PDGFRs)
PDGFRα and PDGFRβ are members of the family of class III receptor tyrosine kinases which also include c-KIT, FLT3, KDR, and c-FMS (reviewed in Ref. [46]). These molecules are characterized by an extracellular ligand-binding domain comprising five immunoglobulin-like structures: a transmembrane (TM) domain, a juxtamembrane (JM) domain, two intracellular tyrosine kinase (TK) domains interrupted by a kinase insert (KI), and a C-terminal domain.47 PDGFRβ is a 190-kDa transmembrane protein expressed
A diagnostic, classification, and treatment algorithm for hypereosinophilia
We have developed a diagnostic algorithm for hypereosinophilia in which detection of the FIP1L1–PDGFRA fusion is a nodal point that generates a potentially useful classification and treatment scheme for eosinophilic disorders (Figure 3(A)). In patients whose work-up is negative for secondary causes of eosinophilia, screening for the FIP1L1–PDGFRA gene fusion could subsequently be undertaken using either RT-PCR or interphase/metaphase FISH. Because testing for FIP1L1–PDGFRA is not widely
Summary
The study of hypereosinophilia was originally rooted in descriptive and morphologic investigations. However, more sophisticated understanding of the molecular network of fusion tyrosine kinase genes in eosinophilic disorders (see Figure 1) now permits a more pathobiologically oriented classification scheme that translates into opportunities for novel therapeutic approaches with imatinib mesylate and other tyrosine kinase inhibitors, and anti-IL-5 antibody therapy.
Investigations have shown the
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Platelet-derived growth factor receptors (PDGFRs) fusion genes involvement in hematological malignancies
2017, Critical Reviews in Oncology/HematologyThree cases of feline hypereosinophilic syndrome treated with imatinib mesilate
2014, Revue Veterinaire CliniqueCitation Excerpt :Alternative therapies for patients failing or not tolerating glucocorticosteroid therapy include cytotoxic agents (such as hydroxyurea and vincristine) and immunomodulatory agents (including ciclosporin), of which interferon-α showed the most promise. Recent diagnostic advances and the development of novel targeted therapies, including the tyrosine kinase inhibitors and humanized monoclonal antibodies, have expanded the armamentarium [1,2,10]. The successful empiric treatment with imatinib mesylate in a human patient with HES refractory to traditional therapy was first reported in 2001.
Eosinophils in Human Disease
2013, Eosinophils in Health and DiseaseICON: Eosinophil disorders
2012, World Allergy Organization JournalContemporary consensus proposal on criteria and classification of eosinophilic disorders and related syndromes
2012, Journal of Allergy and Clinical Immunology