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Cell Mol Life Sci. 2004 Dec;61(23):2912-23.

Oncogenic derivatives of platelet-derived growth factor receptors.

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Wessex Regional Genetics Laboratory, Salisbury, United Kingdom.


Platelet-derived growth factor receptors (PDGFRs) and their ligands, platelet-derived growth factors (PDGFs) play critical roles in mesenchymal cell migration and proliferation. In embryogenesis the PDGFR/PDGF system is essential for the correct development of the kidney, cardiovascular system, brain, lung and connective tissue. In adults, PDGFR/PDGF is important in wound healing, inflammation and angiogenesis. Abnormalities of PDGFR/PDGF are thought to contribute to a number of human diseases, and especially malignancy. Constitutive activation of the PDGFRalpha or PDGFRbeta receptor tyrosine kinases is seen in myeloid malignancies as a consequence of fusion to diverse partner genes, and activating mutations of PDGFRalpha are seen in gastrointestinal tumours (GISTs). Autocrine signalling as a consequence of PDGF-B overexpression is clearly implicated in the pathogenesis of dermatofibrosarcoma protruberans (DFSP) and overexpression of PDGFRs and/or their ligands has been described in many solid tumours. PDGFR signalling is inhibited by imatinib mesylate, and this compound has clear clinical activity in patients with myeloid malignancies, GIST and DFSP.

[Indexed for MEDLINE]

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