Am J Blood Res 2012;2(1):44-56
Review Article
Platelet-derived growth factors and their receptors in normal and malignant
hematopoiesis
Jean-Baptiste Demoulin, Carmen P. Montano-Almendras
Université catholique de Louvain, De Duve Institute, Brussels, Belgium
Received October 27, 2011; accepted November 15, 2011; Epub November 15, 2011; Published January 15, 2011
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 PDGFs were
initially purified from platelets more than 30 years ago, their 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.(AJBR1110005).
Keywords: Receptor tyrosine kinase, hypereosinophilia, signal transduction, imatinib, myeloproliferative disorders, myeloid
neoplasms, chronic eosinophilic leukemia, hypereosinophilic syndrome
Full Text PDF
Address all correspondence to:
Dr. Jean-Baptiste Demoulin
Université catholique de Louvain
De Duve Institute, Brussels, Belgium.
E-mail: jb.demoulin@uclouvain.be
Review Article
Platelet-derived growth factors and their receptors in normal and malignant
hematopoiesis
Jean-Baptiste Demoulin, Carmen P. Montano-Almendras
Université catholique de Louvain, De Duve Institute, Brussels, Belgium
Received October 27, 2011; accepted November 15, 2011; Epub November 15, 2011; Published January 15, 2011
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 PDGFs were
initially purified from platelets more than 30 years ago, their 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.(AJBR1110005).
Keywords: Receptor tyrosine kinase, hypereosinophilia, signal transduction, imatinib, myeloproliferative disorders, myeloid
neoplasms, chronic eosinophilic leukemia, hypereosinophilic syndrome
Full Text PDF
Address all correspondence to:
Dr. Jean-Baptiste Demoulin
Université catholique de Louvain
De Duve Institute, Brussels, Belgium.
E-mail: jb.demoulin@uclouvain.be
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