Fibroblast growth factor receptor and platelet-derived growth factor receptor abnormalities in eosinophilic myeloproliferative disorders
Fibroblast growth factor receptor and platelet-derived growth factor receptor abnormalities in eosinophilic myeloproliferative disorders
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DOI：
10.1159/000140631
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发表时间：
2008-01-01
影响因子：
2.4
通讯作者：
Reiter, Andreas
中科院分区：
文献类型：
--
作者：
Cross, Nicholas C. P.;Reiter, Andreas
编码成纤维细胞生长因子受体1 （FGFR1）和血小板衍生生长因子受体(PDGFR) α或β受体酪氨酸激酶的基因重排在罕见但重要的非典型骨髓增殖性疾病患者中被发现，这些疾病通常但并不总是与嗜酸性粒细胞增多症相关。染色体易位或其他在8p11- 12,4q12或5q31-33的重排产生不同的融合基因，编码具有组成转化活性的嵌合蛋白。目前已知FGFR1有8个伴侣基因，PDGFRA有6个，PDGFRB有17个，存在相当大的分子异质性。绝大多数PDGFRA或PDGFRB融合患者对持续伊马替尼治疗可实现快速持久的完全血液学和分子反应。一个关键的持续挑战是确定绝大多数病因不明的非典型骨髓增生性疾病的分子发病机制，因为这些病例很少能从伊马替尼或其他第二代抑制剂中获益。版权所有(c) 2008 S. Karger AG，巴塞尔。
Rearrangements of the genes encoding the fibroblast growth factor receptor 1 (FGFR1) and platelet-derived growth factor receptors (PDGFR) alpha or beta receptor tyrosine kinases are found in a rare but important subset of patients with atypical myeloproliferative disorders that are usually but not always associated with eosinophilia. Chromosomal translocations or other rearrangements at 8p11-12, 4q12 or 5q31-33 give rise to diverse fusion genes encoding chimaeric proteins with constitutive transforming activity. There is considerable molecular heterogeneity with 8 partner genes currently known for FGFR1, 6 for PDGFRA and 17 for PDGFRB. The vast majority of patients with PDGFRA or PDGFRB fusions achieve rapid and durable complete haematological and molecular responses to sustained imatinib therapy. A key ongoing challenge is to define the molecular pathogenesis of the great majority of atypical myeloproliferative disorders for whom the causative lesion remains unknown, since very few of these cases gain any benefit from imatinib or other second-generation inhibitors. Copyright (c) 2008 S. Karger AG, Basel.