Platelet-derived growth factors and their receptors in normal and malignant hematopoiesis

作者: Carmen P Montano-Almendras , Jean-Baptiste Demoulin

DOI:

关键词: Receptor tyrosine kinasePlatelet-derived growth factor receptorSignal transductionKinase activityReceptorPDGFRAImmunologyPDGFRBMedicineTyrosine-kinase inhibitorCancer research

摘要: Platelet-derived growth factors (PDGF) bind to two closely related receptor tyrosine kinases, PDGF α and β, which are encoded by the PDGFRA PDGFRB genes. Aberrant activation of receptors occurs in myeloid malignancies associated with hypereosinophilia, due chromosomal alterations that produce fusion genes, such as ETV6-PDGFRB or FIP1L1-PDGFRA. Most patients males respond low dose imatinib, is particularly effective against kinase activity. Recently, activating point mutations were also described hypereosinophilia. In addition, autocrine loops have been identified large granular lymphocyte leukemia HTLV-transformed lymphocytes, suggesting new possible indications for inhibitor therapy. Although was initially purified from platelets more than 30 years ago, its physiological role hematopoietic system remains unclear. Hematopoietic defects PDGF-deficient mice reported but appear be secondary cardiovascular placental abnormalities. Nevertheless, acts directly on several cell types vitro, megakaryocytes, platelets, activated macrophages and, possibly, certain subsets eosinophils. The relevance these observations normal human hematopoiesis established.

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