Molecular characterization of the idiopathic hypereosinophilic syndrome (HES) in 35 French patients with normal conventional cytogenetics
Molecular characterization of the idiopathic hypereosinophilic syndrome (HES) in 35 French patients with normal conventional cytogenetics
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DOI：
10.1038/sj.leu.2403722
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发表时间：
2005-05-01
期刊：
影响因子：
11.4
通讯作者：
Preudhomme, C
中科院分区：
文献类型：
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作者：
Roche-Lestienne, C;Lepers, S;Preudhomme, C
特发性嗜酸性粒细胞增多综合征（HES）以原因不明和持续性嗜酸性粒细胞增多为特征，是异质性的，包括几个实体：骨髓增生性形式，其中骨髓谱系涉及间质染色体4 q12缺失，导致FIP 1 L1和PDGFRA基因融合，后者获得酪氨酸激酶活性增加。还有一种淋巴细胞变体，其中嗜酸性粒细胞增多症是继发于原始T淋巴疾病的，这通过循环T细胞克隆的存在来证明。我们通过常规细胞遗传学分析对35例正常核型的HES患者进行了分子表征。TCR γ基因重排表明T克隆性见于11例（31%）患者，FIP 1 L1- PDGFRA通过RT-PCR在6例（17%）35例患者中，谁没有表现出T细胞克隆性的证据。在对伊马替尼有反应的FIP 1 L1 PDGFRA阳性患者中观察到血清类胰蛋白酶水平升高，而在T细胞相关嗜酸性粒细胞增多症中血清IL-5水平未升高。FIP 1 L1- PDGFRA测序显示FIP 1 L1-外显子（10 - 13）中存在分散的断裂点，而断裂点仅限于PDGFRA的外显子12。在29例无FIP 1 L1- PDGFRA的患者中，未检测到PDGFRA/ PDGFRB激活突变;然而，1例患者对伊马替尼有反应。4 q12缺失的FISH分析与FIP 1 L1- PDGFRA RT-PCR数据一致。进一步研究FIP 1 L1- PDGFRA影响细胞的性质将改善HES的分类。
Idiopathic hypereosinophilic syndrome (HES) characterized by unexplained and persistent hypereosinophilia is heterogeneous and comprises several entities: a myeloproliferative form where myeloid lineages are involved with the interstitial chromosome 4q12 deletion leading to fusion between FIP1L1 and PDGFRA genes, the latter acquiring increased tyrosine kinase activity. And a lymphocytic variant, where hypereosinophilia is secondary to a primitive T lymphoid disorder demonstrated by the presence of a circulating T-cell clone. We performed molecular characterization of HES in 35 patients with normal karyotype by conventional cytogenetic analysis. TCR gamma gene rearrangements suggesting T clonality were seen in 11 (31%) patients, and FIP1L1 - PDGFRA by RT-PCR in six (17%) of 35 patients, who showed no evidence of T-cell clonality. An elevated serum tryptase level was observed in FIP1L1 PDGFRA- positive patients responding to imatinib, whereas serum IL-5 levels were not elevated in T-cell associated hypereosinophilia. Sequencing FIP1L1 - PDGFRA revealed scattered breakpoints in FIP1L1-exons ( 10 - 13), whereas breakpoints were restricted to exon 12 of PDGFRA. In the 29 patients without FIP1L1 - PDGFRA, no activating mutation of PDGFRA/ PDGFRB was detected; however; one patient responded to imatinib. FISH analysis of the 4q12 deletion was concordant with FIP1L1 - PDGFRA RT-PCR data. Further investigation of the nature of FIP1L1 - PDGFRA affected cells will improve the classification of HES.