Demoulin Jean-Baptiste, Montano-Almendras Carmen P
Université catholique de Louvain, De Duve Institute Brussels, Belgium.
Am J Blood Res. 2012;2(1):44-56. Epub 2012 Jan 1.
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.
血小板衍生生长因子（PDGF）与两种密切相关的受体酪氨酸激酶——PDGF受体α和β结合，这两种激酶由PDGFRA和PDGFRB基因编码。由于产生融合基因（如ETV6 - PDGFRB或FIP1L1 - PDGFRA）的染色体改变，PDGF受体的异常激活发生在与嗜酸性粒细胞增多相关的髓系恶性肿瘤中。大多数患者为男性，对低剂量伊马替尼有反应，伊马替尼对PDGF受体激酶活性特别有效。最近，在嗜酸性粒细胞增多症中也发现了PDGFRA的激活点突变。此外，在大颗粒淋巴细胞白血病和HTLV转化的淋巴细胞中已鉴定出自分泌环，提示酪氨酸激酶抑制剂治疗可能有新的适应症。尽管PDGF在30多年前最初是从血小板中纯化出来的，但其在造血系统中的生理作用仍不清楚。已有报道称PDGF缺陷小鼠存在造血缺陷，但似乎是继发于心血管和胎盘异常。然而，PDGF在体外可直接作用于几种造血细胞类型，如巨核细胞、血小板、活化的巨噬细胞，可能还有某些淋巴细胞亚群和嗜酸性粒细胞。这些观察结果与正常人类造血的相关性仍有待确定。
