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Am J Blood Res. 2012;2(1):44-56. Epub 2012 Jan 1.

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

Author information

1
Université catholique de Louvain, De Duve Institute Brussels, Belgium.

Abstract

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

KEYWORDS:

Receptor tyrosine kinase; chronic eosinophilic leukemia; hypereosinophilia; hypereosinophilic syndrome; imatinib; myeloid neoplasms; myeloproliferative disorders; signal transduction

PMID:
22432087
PMCID:
PMC3301440

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